tbuckley/cabot-search huggingface dataset:
Abstract 2827: A platform to study metastatic cancer.
Authors: Andrew D. Wong, Peter C. Searson
Journal: Cancer Research (2013)

Abstract Metastasis is responsible for over 90% of cancer related deaths. While significant advances in visualizing metastasis have been made in vivo, the details of the biological and physical processes that govern invasion and intravasation remain poorly understood. The difficulty in studying metastasis stems from the complexity of the interface where invasion and intravasation take place, between the tumor's local tissue microenvironment and the vascular system. To elucidate the mechanistic events taking place during invasion and intravasation, we have developed a platform that positions tumor cells adjacent to an artificial vessel embedded in an extracellular matrix (ECM). Using live-cell, fluorescence microscopy, we study the complex interplay between highly metastatic cancer cells and a functional artificial microvessel lined with endothelial cells during tumor migration and intravasation. We hypothesize that an engineered platform that recapitulates the interactions between a tumor and a physiologically relevant artificial vessel within an extracellular matrix will allow the systematic study of the physical and biological properties that regulate invasion and intravasastion. Since there remain many gaps in our understanding of the biology and physics of invasion and intravasation, further insight into these poorly understood processes may provide new strategies to prevent the spread of cancer and reduce the high mortality rates associated with metastasis. Citation Format: Andrew D. Wong, Peter C. Searson. A platform to study metastatic cancer. [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 2827. doi:10.1158/1538-7445.AM2013-2827
Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat—angiogenesis and angioma formation
Authors: Ernst R Schwarz, Mark T Speakman, Mike Patterson, Sharon S Hale, Jeffrey M Isner, Laurence H Kedes, Robert A Kloner
Journal: Journal of the American College of Cardiology (2000)
Pope claims that condoms exacerbate HIV and AIDS problem
Authors: B. Roehr
Journal: BMJ (2009)

Pope Benedict XVI has disparaged the use of condoms as a tool to rein in the AIDS pandemic. “You can’t resolve it with the distribution of condoms,” the pope told reporters travelling with him on his first trip to Africa. “On the contrary, it increases the problem.”

The 81 year old pontiff said that abstinence and fidelity within marriage were the solutions in the fight against AIDS.

Numerous African clergy and lay people have long urged the pope to ease the Catholic church’s prohibition on condom use within the context of HIV prevention.

Criticisms of the …
Medical Care for Terrorists—To Treat or Not to Treat?
Authors: Benjamin Gesundheit, Nachman Ash, Shraga Blazer, Avraham I. Rivkind
Journal: The American Journal of Bioethics (2009)

With the escalation of terrorism worldwide in recent years, situations arise in which the perpetration of violence and the defense of human rights come into conflict, creating serious ethical problems. The Geneva Convention provides guidelines for the medical treatment of enemy wounded and sick, as well as prisoners of war. However, there are no comparable provisions for the treatment of terrorists, who can be termed unlawful combatants or unprivileged belligerents. Two cases of severely injured terrorists are presented here to illustrate the dilemmas facing the medical staff that treated them. It is suggested that international legal and bioethical guidelines are required to define the role of the physician and auxiliary medical staff vis a vis injured terrorists. There are extreme situations where the perpetration of violence and the defense of human rights come into conflict, leading to serious ethical and psychological discord. Terrorists, using violence to create fear in order to further their political objectives, might require life-saving medical care if injured during the course of their terror activities.
Negative diastolic pressure in the intact canine right ventricle. Evidence of diastolic suction.
Authors: H N Sabbah, P D Stein
Journal: Circulation Research (1981)

To determine whether the canine right ventricle (RV) can develop a negative diastolic pressure indicative of suction, RV pressure was measured in 15 dogs, with catheter-tip micromanometers. Six dogs were studied only with the chest closed. In these dogs, intrapleural pressure was measured medially (near the heart) in four and laterally in two. In nine dogs, RV pressure was evaluated with the chest closed and after the chest had been opened. In all dogs, with the chest closed, minimal RV diastolic pressure during expiration was negative, -4.8 +/- 0.3 mm Hg. The lowest diastolic pressures occurred during early diastole. Intrapleural pressure during expiration was never this low. Intrapleural pressure measured medially in four dogs was positive during expiration (1.0 +/- 0.6 mm Hg). In the two dogs which it was measured in the lateral pleural space, it was somewhat negative during expiration (-2.5 and -1.3 mm Hg, respectively). After the chest had been opened (nine dogs) minimal RV pressure during early diastole was negative in six dogs and positive in three (range: -1.8 to 0.8 mm Hg). These results indicate that the negative RV diastolic pressure during expiration did not result from a negative intrathoracic pressure. It appears that the RV during early diastole can create a sucking effect which may contribute to the filling process.
Molecular Screening for Cervical Cancer — Time to Give up Pap Tests?
Authors: Carolyn D. Runowicz
Journal: New England Journal of Medicine (2007)

In 1943, Papanicolaou and Traut published their famous monograph on vaginal cytology as a screening method for uterine cancer.1 Since then, the Papanicolaou (Pap) smear has become the most commonly used method to screen for cervical neoplasia, and it is the best screening tool ever introduced for any cancer. The remarkable success achieved in preventing cervical cancer is largely attributable to cytologic screening tests. With the introduction of organized cervical cytologic-screening programs, the incidence of cervical cancer has been dramatically reduced. However, high-quality cytology-based screening programs require highly trained personnel and some specialized equipment. Cytologic screening tests for cervical neoplasia . . .
IRON AND COPPER IN THE TREATMENT OF ANEMIA IN CHILDREN
Authors: MILTON SMITH LEWIS
Journal: JAMA (1931)

In May, 1928, Hart, Steenbock, Waddell and Elvehjem<sup>1</sup>reported a series of observations on the rat in which they showed that iron was inadequate to bring about regeneration of hemoglobin, but on the addition of a small amount of copper regeneration took place rapidly. The importance of the rôle of copper as an adjunct to iron was discovered only after careful elimination of other possible factors. Since then they<sup>2</sup>have shown conclusively that copper plays a unique part in hemoglobin response. McHargue, Healy and Hill<sup>3</sup>state that copper has an important function in the formation of hemoglobin. Elden, Sperry, Robscheit-Robbins and Whipple<sup>4</sup>admit that certain metals and their salts when added to the standard diet have a distinct influence and increase the production of hemoglobin. The feeding of copper and iron combined may at times have an unusually favorable effect or again may not exceed the
Low avidity anti-citrullinated protein antibodies (ACPA) are associated with high radiographic progression in rheumatoid arthritis
Authors: P. Suwannalai, H.U. Scherer, A. Ioan-Facsinay, Jol-van der Zijde, M.J.D. van Tol, A.H. Van der Helm-van Mil, R. Knevel, T.W.J. Huizinga, R.E.M. Toes, L.A. Trouw
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Anti-citrullinated protein antibodies (ACPA) are specific for Rheumatoid Arthritis (RA). Their presence is predictive for development to RA and they have been implicated in disease-pathogenesis in animal studies. The biology of the ACPA response and its consequence are poorly studied in humans. We have shown that ACPA display a relatively low avidity which correlated with the absence of avidity maturation in time. <h3>Materials and methods</h3> We determined the avidity of the ACPA response and the impact on clinical phenotype. <h3>Results</h3> Although of low avidity, variation in ACPA-avidity was observed between patients. In this study we show that the avidity of ACPA is associated with clinical outcomes. Intriguingly, the presence of low avidity ACPA and not higher avidity ACPA is associated with higher rate of joint destruction as measured by erosions and joint space narrowing. In-vitro experiments support the idea that low avidity ACPA may contribute more to tissue pathology because of a better tissue-penetration capacity. Conclusions Within ACPA positive individuals it is the patients with the lowest ACPA avidities that display the most severe joint damage.
Relation between Bronchial Reactivity to Antigen in Vivo and Serum IgE and IgG<sub>2a</sub>Antibody Levels in Rats
Authors: Magnus Dahlbäck, Romain Pauwels, Herve Bazin, Håkan Bercstrand
Journal: Allergy (1982)

Sprague Dawley rats were immunized with graded doses of ovalbumin (O A) together with alum. The capacity of the animals to produce a bronchial anaphylactic response to intravenous antigen challenge was related to serum OA‐IgE and OA‐IgG 2a antibody levels estimated by radioimmunossay. A significant correlation between bronchial anaphylactic response capacity and OA‐IgE antibody levels was found under a few, but not all, of several carefully chosen experimental conditions. No correlation was demonstrable between the in vivo reactivity of the animals and their serum levels of OA‐specific IgGg 2a antibodies.
Cross-sectional Study of a Community With Exceptional Exposure to DDT
Authors: Kathleen Kreiss
Journal: JAMA (1981)

The geometric mean level of total DDT in serum samples (76.2 ng/mL) from 499 persons living downstream from a defunct DDT-manufacturing plant was several times the national geometric mean (15.0 ng/mL). DDE isomers, metabolites of DDT, accounted for an average of 86.7% of total DDT. Total DDT levels increased with age, even when controlled for other independent variables also significantly associated with DDT: race, sex, fish consumption, years of residence, socioeconomic status, alcohol consumption, and serum triglyceride levels. Fish consumption, the second strongest determinant of DDT level, had one third the predictive power of age. Total DDT levels were not associated with specific illness or ill health. However, total DDT levels were positively associated with levels of serum cholesterol, triglyceride, and γ-glutamyl transpeptidase. The finding that serum DDE levels increase with age suggests that no equilibrium in body burden has been reached or that pharmacokinetics or serum/adipose partition may vary with age. (<i>JAMA</i>1981;245:1926-1930)
In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas
Authors: Olivier Manches, Gabrielle Lui, Laurence Chaperot, Rémy Gressin, Jean-Paul Molens, Marie-Christine Jacob, Jean-Jacques Sotto, Dominique Leroux, Jean-Claude Bensa, Joël Plumas
Journal: Blood (2003)

Abstract To assess the sensitivity of primary non-Hodgkin lymphoma cells to rituximab-mediated cytotoxicity, we compared the potency of several rituximab-mediated killing mechanisms on fresh lymphoma cells. All lymphoma cells tested were equally sensitive to antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-mediated phagocytosis of tumor cells, and rituximab-induced apoptosis. However, they were differentially lysed by complement-dependent cytotoxicity (CDC). We found that taking into account both CD20 and complement regulatory protein expression on tumor cells could predict CDC sensitivity in vitro. Importantly, the sensitivity of lymphoma cells to CDC was consistent with the reported different clinical response rates of lymphomas: rituximab induced high CDC killing of follicular lymphoma cells, whereas mantle cell lymphoma and diffuse large cell lymphoma cells were moderately sensible to CDC, and small lymphocytic lymphoma cells were almost all resistant. We propose that CDC is a determinant mechanism of rituximab-induced killing in vivo. Poor sensitivity to CDC in vitro might predict a poor clinical response, whereas high sensitivity to CDC would only indicate a likelihood of response to rituximab treatment.
Elevated Presence of Basophils in Chronic Rhinosinusitis with Nasal Polyposis
Authors: Mahboobeh Mahdavinia, Kathryn E. Hulse, Roderick Carter, James Norton, Lydia Suh, Atsushi Kato, Anju Peters, Rakesh Chandra, David Conley, Robert Kern, Bruce Tan, Leslie C. Grammer, Lawrence B. Schwartz, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2013)
The Spectrum of Septic Encephalopathy
Authors: Leonid A. Eidelman, Debby Putterman, Chaim Putterman, Charles L. Sprung
Journal: JAMA (1996)

To determine whether the severity of septic encephalopathy is correlated with gram-negative bacteremia and mortality and whether there exists a single or combination of metabolic derangements(s) that cause septic encephalopathy.Prospective case series in an academic medical center.Fifty patients selected according to clinical and laboratory criteria for severe sepsis. The criteria included temperature, heart rate, respiratory rate, and hypotension and/or signs of systemic hypoperfusion.A single or combination of metabolic and laboratory derangements and organ failures, three different methods to grade the severity of septic encephalopathy, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, gram-negative bacteremia and infection, and mortality.Encephalopathy was associated with an increase in mortality when graded by the Glasgow Coma Score; a score of 15 had 16% mortality, 13 to 14 had 20%, 9 to 12 had 50%, and 3 to 8 had 63% mortality (P < .05). Bacteremia was associated with encephalopathy; 13% of septic patients without encephalopathy vs 59% of patients with encephalopathy had bacteremia (P < .001) when graded by altered mental status. Septic encephalopathic patients had elevated serum urea nitrogen and bilirubin levels, increased APACHE II scores, and a higher incidence of renal failure.The severity of septic encephalopathy correlated with mortality, bacteremia, and renal and hepatic dysfunction. The Glasgow Coma Score is a useful tool for characterizing septic encephalopathy. Considerable variations can be found according to different criteria used to classify septic encephalopathy.
Miraculous deliverance of Anne Green.
Authors: S G Braye, G Guy
Journal: BMJ (1983)

<h3>BACKGROUND AND PURPOSE:</h3> Successful endovascular treatment of intracranial aneurysms requires understanding the exact relationship of implanted devices to the aneurysm, parent artery, and other branch vessels during the treatment. Intraprocedural C-arm CT imaging has been shown to provide such information. However, its repeated use is limited due to increasing radiation exposure to the patient. The goal of this study was to evaluate a new volume-of-interest C-arm CT imaging technique, which would provide device-specific information through multiple 3D acquisitions of only the region of interest, thus reducing cumulative radiation exposure to the patient. <h3>MATERIALS AND METHODS:</h3> VOI C-arm CT images were obtained in 28 patients undergoing endovascular treatment of intracranial aneurysms. VOI images were acquired with the x-ray source collimated around the deployed device, both horizontally and vertically. The images were reconstructed by using a novel prototype robust reconstruction algorithm to minimize truncation artifacts from double collimation. The reconstruction accuracy of VOI C-arm CT images was assessed quantitatively by comparing them with the full-head noncollimated images. <h3>RESULTS:</h3> Quantitative analysis showed that the quality of VOI C-arm CT images is comparable with that of the standard Feldkamp, Davis, and Kress reconstruction of noncollimated C-arm CT images (correlation coefficient = 0.96 and structural similarity index = 0.92). Furthermore, 91.5% reduction in dose-area product was achieved with VOI imaging compared with the full-head acquisition. <h3>CONCLUSIONS:</h3> VOI imaging allows multiple 3D C-arm CT acquisitions and provides information related to device expansion, parent wall apposition, and neck coverage during the procedure, with very low additional radiation exposure to the patient.
High-efficiency Transduction of the Mouse Retina by Tyrosine-mutant AAV Serotype Vectors
Authors: Hilda Petrs-Silva, Astra Dinculescu, Qiuhong Li, Seok-Hong Min, Vince Chiodo, Ji-Jing Pang, Li Zhong, Sergei Zolotukhin, Arun Srivastava, Alfred S Lewin, William W Hauswirth
Journal: Molecular Therapy (2008)

Vectors derived from adeno-associated viruses (AAVs) have become important gene delivery tools for the treatment of many inherited ocular diseases in well-characterized animal models. Previous studies have determined that the viral capsid plays an essential role in the cellular tropism and efficiency of transgene expression. Recently, it was shown that phosphorylation of surface-exposed tyrosine residues from AAV2 capsid targets the viral particles for ubiquitination and proteasome- mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo. Because the tyrosine residues are highly conserved in other AAV serotypes, in this study we evaluated the intraocular transduction characteristics of vectors containing point mutations in surface- exposed capsid tyrosine residues in AAV serotypes 2, 8, and 9. Several of these novel AAV mutants were found to display a strong and widespread transgene expression in many retinal cells after subretinal or intravitreal delivery compared with their wild-type counterparts. For the first time, we show efficient transduction of the ganglion cell layer by AAV serotype 8 or 9 mutant vectors, thus providing additional tools besides AAV2 for targeting these cells. These enhanced AAV vectors have a great potential for future therapeutic applications for retinal degenerations and ocular neovascular diseases. Vectors derived from adeno-associated viruses (AAVs) have become important gene delivery tools for the treatment of many inherited ocular diseases in well-characterized animal models. Previous studies have determined that the viral capsid plays an essential role in the cellular tropism and efficiency of transgene expression. Recently, it was shown that phosphorylation of surface-exposed tyrosine residues from AAV2 capsid targets the viral particles for ubiquitination and proteasome- mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo. Because the tyrosine residues are highly conserved in other AAV serotypes, in this study we evaluated the intraocular transduction characteristics of vectors containing point mutations in surface- exposed capsid tyrosine residues in AAV serotypes 2, 8, and 9. Several of these novel AAV mutants were found to display a strong and widespread transgene expression in many retinal cells after subretinal or intravitreal delivery compared with their wild-type counterparts. For the first time, we show efficient transduction of the ganglion cell layer by AAV serotype 8 or 9 mutant vectors, thus providing additional tools besides AAV2 for targeting these cells. These enhanced AAV vectors have a great potential for future therapeutic applications for retinal degenerations and ocular neovascular diseases.
Effect of radiation on the human reproductive system.
Authors: A L Ogilvy-Stuart, S M Shalet
Journal: Environmental Health Perspectives (1993)

Irradiation may have a profound effect on reproductive function. The schedule of the delivered irradiation (total dose, number of fractions, and duration) is an important determinant of the radiobiological effect on the tissues involved and varies among different tissues and organs. Irradiation to the central nervous system may affect the timing of the onset of puberty, result in hyperprolactinemia, or cause gonadotropin deficiency if the hypothalamic-pituitary axis is involved in the radiation field. Direct irradiation to the testis will, in lower doses, affect the germinal epithelium: doses of irradiation greater than 0.35 Gy cause aspermia, which may be reversible. The time taken for recovery increases with larger doses; however, with doses in excess of 2 Gy aspermia may be permanent. At higher radiation doses (> 15 Gy), Leydig cell function will also be affected. In addition to radiation dose, the vulnerability of the testis is dependent on the age at irradiation and the pubertal status of the male. In the female, the response of the ovary to the effects of irradiation varies with age as well as dose, and separation of ovarian dysfunction into hormonal and fertility effects is not clearcut. An ovarian dose of 4 Gy may cause a 30% incidence of sterility in young women, but 100% sterility in women over 40 years of age. Pelvic irradiation may also have a profound effect on the uterus, with arrested growth in the prepubertal girl, and failure of uterine expansion during pregnancy with subsequent miscarriages and premature labor.
Cigarette smoking in pregnancy and fetal hyperviscosity.
Authors: P C Buchan
Journal: BMJ (1983)

The effects of maternal cigarette smoking on fetal blood viscosity and its major determinants were investigated in an effort to determine if there might be a relation between the intrauterine growth retardation associated with cigarette smoking and fetal hyperviscosity.  Blood was collected from the umbilical vein at birth in 40 infants born to mothers who had smoked more than 20 cigarettes a day throughout pregnancy and from 40 matched nonsmoking controls.  Blood and plasma viscosity packed cell volume plasma fibrinogen concentration and erythrocyte deformability were measured by standard techniques and statistical comparison of the differences in means between the 2 groups made using Students t test.  Cigarette smoking was associated with a 30% increase in fetal blood viscosity this rise being compounded of a 12% increase in packed cell volume and an 18% fall in erythrocyte deformability.  Neither plasma viscosity nor plasma fibrinogen values were altered.  The mean birth weight was 318 gm lower in infants born to smoking mothers.  When adult smokers become pregnant the large physiological variation in blood viscosity factors obscure the effects of smoking in maternal blood.  This is not the case in the fetus.  In the extensive capillary microcirculation of the fetal placental villi raised blood viscosity and reduced erythrocyte deformability would be apt to reduce blood flow significantly in accordance with Poiseuilles law.  Reduced intravillus perfusion would combine with reduced intervillus blood flow on the maternal side of the placenta owing to the effects of nicotine and with the already reduced oxygen availability in both maternal and fetal blood to cause fetal hypoxia stimulating fetal erythropoiesis with a further increase in blood viscosity leading to a vicious circle of decreasing flow and further hypoxia.  The study indicates a new pathogenic pathway for the deleterious effects of maternal cigarette smoking on fetal growth and development in pregnancy.