tbuckley/cabot-search huggingface dataset:
Abstract P3-05-01: “VISA” Nanopaticles to Breast Cancer In Vitro and in Living Imaging Animal Models
Authors: X Xie, W Wei, J Guo, X Xiao, X Xie, Y Kong, J Tang, P Liu, X Wang, N. Lv
Journal: Cancer Research (2010)

Abstract Development of cancer gene therapy has been hampered by the fact that there are no effective cancer-specific expression vectors available, which is critical for improving therapeutic efficacy and reducing toxicity in clinics. To overcome this problem, we recently developed a safe and effective strategy fro targeting a potent pro-apoptotic gene (BikDD) to the pancreatic tumors (Xie et al. Cancer Cell, 2007), lung cancer (Sher et al. Oncogene, 2009) and ovarian cancer (Xie et al. Molecular Cancer Therapeutics, 2009). A VISA system (VP16-Gal4-WPRE integrated systemic amplifier) was engineered by using the two-step transcriptional amplification (TSTA) system and the posttranscriptional regulatory element of the woodchuck hepatitis virus (WPRE). The VISA system can boost the activity of cancer-specific promoters by an average of 600-800-folds compared to their basal levels. C-VISA (CCKAR-VISA) nanoparticles transcriptionally targets transgene expression effectively to pancreatic tumors in vivo. C-VISA-BikDD nanoparticles was shown to be highly effective in reducing tumor burden and increasing animal survival rate in orthotopic pancreatic cancer models which is moving into clinical trials at University of Texas M.D. Anderson Cancer Center, USA. In the current study, we identified hTERT(human telomerase reverse transcriptase), survivin, β-cateinin, claudin-4, and FASN (fatty acid synthase) promoters as breast cancer-selective promoters, and amplified their activity to hundreds of folds greater by the “VISA” system(called x-VISA) without loss of their specificity. Very importantly, the x-VISA promoters were also robust in the primary cultured breast cancer cells, with 42.5 %-65% of the CMV promoter, while retaining stringent pancreatic cancer specificity. x-VISA was also shown to target expression of firefly luciferase to MDA-MB-468 xenografts in an orthotopic mouse model, confirmed by noninvasive imaging with an Xenogen IVIS™ imaging system and measuring with a luminometer. The cancer-specific index was 35-60 for x-VISA-Luc and 0.01 for CMV-Luc in vivo. We further demonstrated significant antitumor activity of targeted BikDD expression driven by nanoparticles of the hTERT-VISA-BikDD vectors in Her-2-negative and-positive and triple-negative breast cancer cell lines in vitro, and in multiple breast cancer models of living imaging by the Xenogen IVIS imaging system with limited toxicity. In addition, treatment with hTERT-VISA-BikDD nanoparticles plus lapatinib or produces evident combinational therapeutic efficacy, which is likely due to the ability of lapatinib to promote apoptosis of Her-2-overexpressing breast cancer cells. Thus, our newly developed hTERT-VISA-BikDD nanoparticles are an innovative strategy for targeted antitumor effects of Her-2-negative, Her-2-positive and triple-negative breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-05-01.
The Coxibs, Selective Inhibitors of Cyclooxygenase-2
Authors: Garret A. FitzGerald, Carlo Patrono
Journal: New England Journal of Medicine (2001)

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used to treat arthritis, menstrual pain, and headache. Although they are effective, their long-term use is limited by gastrointestinal effects such as dyspepsia and abdominal pain and, less often, gastric or duodenal perforation or bleeding. Development of the coxibs, a new group of antiinflammatory drugs, represents a response to the unsatisfactory therapeutic profile of NSAIDs. Both groups of drugs inhibit prostaglandin G/H synthase, the enzyme that catalyzes the transformation of arachidonic acid to a range of lipid mediators, termed prostaglandins and thromboxanes (Figure 1). However, whereas NSAIDs inhibit the two recognized forms of the . . .
Magnitude of CD8 cell reactivity with a peptide pool is comparable to the sum of responses by individual peptides
Authors: Tameem Ansari, Wenji Zhang, Ioana Moldovan, OLeg Targoni, Ramu A Subbramanian, Paul V Lehmann
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides within the pool that are restricted by the same HLA allele, however, will compete for HLA binding displacing each other. Therefore, how much T cell reactivity goes undetected when one
Joan Ellen Maude Watts (née Lambert)
Authors: R. W E Watts
Journal: BMJ (2006)

​FormerFormer consultant obstetrician and gynaecologist Barking and King George V Hospitals, London (b 1918; q Royal Free Hospital 1943; FRCOG), died from cerebrovascular disease on 27 March 2006.




Figure 1




Joan's early posts included house jobs at the Royal Buckingham Hospital, Aylesbury, and house officer and registrar posts at the Mother's Hospital, Clapton; South London Hospital for Women; and Nottingham Women's Hospital. She was involved, with the late Dr Helen Mackay, in the early development of modern treatment for Rhesus incompatibility. She was skilled in difficult obstetric manoeuvres before caesarean section was as widely practised as today, thinking current rates unnecessarily high. She leaves a husband, Richard; a son, also Richard; and two grandchildren.
A NEW APPARATUS FOR THE TREATMENT OF FRACTURE OF THE INFERIOR MAXILLA.Paper read before the Colorado State Medical Society, June 23, 1894.
Authors: CLAYTON PARKHILL
Journal: JAMA (1894)

Last October I was consulted by Mr. C., who gave the history of having been sandbagged the night before. The right side of his face and the parotid region presented evidence of serious contusion. The mouth was open and fixed, giving him the appearance of having a dislocation of the jaw. The incisors were separated about three-quarters of an inch, the posterior molars being in contact. There was no lateral displacement. On examination under an anesthetic, I found a fracture of the neck of the jaw. Crepitue was marked. There was apparently no displacement of the upper fragment. Reduction was effected very easily, the teeth coming into perfect articulation. A gutta-percha splint was molded to the jaw, and attached by tapes to a cap covering the head, making an apparatus similar to what is known as the French Dressing. No sooner had the influence of the anesthetic passed away than
Deaths on the liver transplant waiting list: An analysis of competing risks
Authors: Ray W. Kim, Terry M. Therneau, Joanne T. Benson, Walter K. Kremers, Charles B. Rosen, Gregory J. Gores, Rolland E. Dickson
Journal: Hepatology (2006)

The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (P = .25) or blood type (P = .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (P < .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality. In conclusion, the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation.
Nontuberculous mycobacterial infections of the skin: A retrospective study of 25 cases
Authors: Roni Dodiuk-Gad, Pavel Dyachenko, Michael Ziv, Ayelet Shani-Adir, Yehudit Oren, Saul Mendelovici, Jan Shafer, Bibiana Chazan, Raul Raz, Yoram Keness, Dganit Rozenman
Journal: Journal of the American Academy of Dermatology (2007)
Preservation of Sensation in a Cutaneous Vascular Malformation in Lepromatous Leprosy
Authors: Thomas D. Sabin
Journal: New England Journal of Medicine (1970)

THE remarkably stereotyped distribution of motor and sensory deficits in lepromatous leprosy has been attributed to a wide variety of factors, including the entrapment of the enlarged nerves, the density of nerve endings in different skin areas and the degree of exposure of involved nerves to chronic trauma. The case reported below indicates that variations in surface temperature may affect the pattern of sensory loss in lepromatous leprosy. The superficial tissues of the body have been observed to bear the brant of the pathologic changes in lepromatous leprosy. Thus, clinically, abnormalities are most frequently noted in the skin, anterior third . . .
The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: A study using a newin vitro model of isolated intra-arterially perfused gallbladder
Authors: Stefano Ginanni Corradini, Cristina Ripani, Paola Della Guardia, Luca Giovannelli, Walter Elisei, Alfredo Cantafora, Massimo Codacci Pisanelli, Giovanni Domenico Tebala, Gennaro Nuzzo, Alessandro Corsi, Adolfo Francesco Attili, Livio Capocaccia, Vincenzo Ziparo
Journal: Hepatology (1998)

In this study, we first developed and validated a new in vitro isolated, intra-arterially perfused, gallbladder model and then applied the method to investigate the absorption of biliary lipids by the gallbladder wall and the effect of this process on the composition of human bile. Oxygenated and glucose-added buffer was perfused through the cystic artery to maintain organ viability. A standard pooled natural bile, radiolabeled with H3-cholesterol and C14-palmitoyl-linoleoyl-phosphatidylcholine, was instilled in the lumen via a cystic duct catheter. Changes in bile volume and lipid concentrations were monitored at time intervals to evaluate the disappearance of lipids from bile caused by gallbladder absorptive function. Organ viability was demonstrated by stable lactate dehydrogenase (LDH) organ release and oxygen consumption throughout the experiments. In the pig, disappearance rates of lipids from bile were similar in vitro and in vivo, demonstrating the validity of the isolated in vitro model for functional studies. By applying our in vitro isolated preparation to the human gallbladder, we found that 23% of cholesterol and 32% of phosphatidylcholine, but only 9% of bile salts, disappeared from bile in 5 hours. As a consequence, at the end of the experiments, cholesterol (P < .05) and phospholipid (P < .05) molar percentages were significantly reduced, while the bile salt (P < .05) molar percentage was significantly increased with respect to values at the beginning of the studies. Our findings are of pathophysiological relevance and support the concept that the human gallbladder modifies the relative composition of biliary lipids in such a way as to increase cholesterol solubility in bile.
Abstract 4767: Neo-peptides from gene fusions as cancer vaccine antigens
Authors: Hojoon Lee, John-Charles Rodenberry, Kristen Day, Jose Cano-Buendia, Felicia Craciunescu, Jean-Charles Chapuis, Phillip Stafford, Kathryn Sykes, Patricia E. Carrigan, Stephen A. Johnston
Journal: Cancer Research (2010)

Abstract Background: Of all possible sources of antigens for cancer vaccines, frameshift (FS) peptides are attractive in that they may represent neo-antigens. FS peptides may be induced by insertions/deletions or by chimeric transcripts that result from mis-splicing, chromosomal translocations or trans-splicing of mRNA. Aim: In order to discover FS neo-antigens, we have taken a bioinformatical approach at identifying tumor specific, neo-peptides that are generated when chimeric transcripts are translated. Specifically we have focused our attention on identifying chimeric transcripts that create a frameshift when the exons of two different genes are joined. As a result of this gene fusion, approximately 50% of the time a frameshift occurs thus creating a neo-peptide. Method: In order to quickly identify these types of transcripts that are specific to cancer and not present in normal tissue, we have developed an algorithm that can be used to screen publically available databases and high-throughput sequencing data. As proof of principle we have applied this algorithm to the NCBI Expressed Sequence Tag database that contains cDNA sequencing information for normal and cancer tissues. Results: Based on this approach, we have identified and validated 35 chimeric transcripts that are present in breast cancer cell lines and in primary breast tumors. In addition, 9 chimeric transcripts are also present in seven different pancreatic cancer cell lines. Of the 35 chimeric transcripts, 11 chimeric transcripts produce frameshift peptides that are at least nine amino acids or longer and are predicted by SYFPEITHI and Rankpep to be immunogenic and capable of being presented in the most frequent human class I MHC alleles. Moreover, our analyses also identified chimeric transcripts that have already been confirmed by 454 sequencing for breast and prostate cancer. Discussion: Defining the chimeric transcriptome in both healthy and cancer patients could be critical for the development of new therapeutic agents. Of more interest to us, is their potential contribution to a prophylactic cancer vaccine. (This work is supported by a DoD Innovator Award and a Keck Foundation grant to SAJ) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4767.
Urinary Excretion of Human Chorionic Gonadotrophin in Patients with Hyperemesis Gravidarum
Authors: D. V. I. Fairweather, J. A. Loraine
Journal: BMJ (1962)

Th. aetiology of hyperemesis gravidarum has been the subject of much speculation and very little factual information. The possibility that ovarian and placental hormones may play some part has been suggested by various investigators (Anselmino and Hoffmann, 1936; Rakoff, 1940; Schoeneck, 1942), but at the time of writing little or no reliable information was available in the literature on the levels of such hormones in the body fluids of patients with this disease. In a clinical study of a series of patients with hyperemesis gravidarum (Fairweather, 1961, unpub lished) the duration of pregnancy at the time of onset of symptoms was noted and it was observed that most subjects presented at a time during pregnancy at which the levels of human chorionic gonadotrophin (H.C.G.) in blood and urine might be expected to be at their maximum. The possibility that patients suffering from hyperemesis might be unduly sensitive to H.C.G. was also considered, and a simple sensitivity reaction was devised to test this hypothesis (see Appendix). The preliminary results obtained suggested that sensitivity to H.C.G. might play some part in the aetiology of the disease, and, accordingly, it was decided to perform urinary H.C.G. assays in a series of patients with hyperemesis gravidarum and to attempt to correlate the assay results obtained with the clinical picture of the disease. The present report describes studies in a total of 90 patients suffering from hyperemesis gravidarum. The cases were observed in two centres-Aberdeen and Newcastle upon Tyne-by one of us (D. V. I. F.). The study began in November, 1957; the last patient was admitted to the series in March, 1960, and was delivered in October, 1960. The H.C.G. excretion in the hyperemesis patients was compared with that in a series of normally pregnant women at comparable stages of pregnancy. The  control  subjects were also observed in two centres, in Edinburgh by J. A. L. from 1947 to 1949 and in Newcastle upon Tyne by D. V. I. F. during 1960. The results obtained in the Edinburgh series have been reported previously (Loraine, 1949a, 1950a). For the purpose of this study hyperemesis gravidarum is defined as vomiting in pregnancy, occurring up to and including the 20th week of gestation, unassociated with conditions coincidental to the pregnancy such as pyelitis, appendicitis, etc., and of such severity as to require the admission of the patient to hospital. Materials and Methods
Effects of sulphasalazine (Salazopyrin) on faecal flora in patients with inflammatory bowel disease
Authors: B. West, R. Lendrum, M. J. Hill, G. Walker
Journal: Gut (1974)

The faecal flora of 21 patients with proctocolitis and five patients with Crohn9s disease of the large bowel was examined both while sulphasalazine was being administered and during control periods. Patients with proctocolitis and Crohn9s disease who were not receiving sulphasalazine had a similar flora which did not differ in any way from the normal. The effect of sulphasalazine was to decrease the numbers of opalescent-negative clostridia, enterobacteria, and total non-sporing anaerobes. It is suggested that this antibacterial effect of sulphasalazine, which has not been previously demonstrated, may be related to the beneficial effects of this drug in proctocolitis and should be investigated further.
Advantages and disadvantages of neonatal circumcision
Authors: R. S. Van Howe
Journal: JAMA (1997)

To the Editor.  —That the article by Dr Laumann et al 1 documented differences in the sexual practices of men with regard to circumcision status is not surprising. Surgical removal of the prepuce results in the loss of the majority of fine-touch neuroreceptors found in the penis, 2 leaving only the exposed glans, which is innervated with free nerve endings that can only sense deep pressure and pain. 3   A hypothesis is needed to explain the findings of Laumann et al in light of the known neurohistology. We suggest that a penis with foreskin and its full complement of neuroreceptors may make heterosexual coitus more satisfying, thereby making the man less likely to seek out alternate forms of stimulation. The only portion of the prepuce remaining in a man with surgically altered genitalia is the remnant between the coronaand the scar. While there are some fine-touch receptors in this tissue, the most sensitive
Treatment of Acute Otitis Media
Authors: Victor Goodhill
Journal: JAMA (1977)

To the Editor.—  In the CLINICAL NOTE of Crosson et al (2362778, 1976) on acute otitis media, a recommendation is made for diagnostic needle aspiration of the middle ear in suspected resistant infections. While there is a place for tympanocentesis in other otologic diagnostic problems, it is not the procedure of choice in acute otitis media in a 2-year-old infant with no response to ten days of ampicillin or any other antibiotic therapy. The issue in this case is not that of a bacteriologic-antibiotic debate but the question of proper therapy for otitis media that does not respond rapidly (three to four days) to antibiotic therapy. Myringotomy is indicated in such cases.  Undue reliance on antibiotic therapy in tympanic membranes described as hemorrhagic and bulging can be and frequently is followed by complications. Mastoiditis and intracranial complications (eg, otitic meningitis, brain abscess, and otitic hydrocephalus) have not disappeared in the antibiotic
Targeted drug delivery and cross-linking induced apoptosis with anti-CD37 based dual-ligand immunoliposomes in B chronic lymphocytic leukemia cells
Authors: Bo Yu, Yicheng Mao, Yuan Yuan, Chaofang Yue, Xinmei Wang, Xiaokui Mo, David Jarjoura, Michael E. Paulaitis, Robert J. Lee, John C. Byrd, L. James Lee, Natarajan Muthusamy
Journal: Biomaterials (2013)
Respiratory side effects of beta-blockers.
Authors: K N Palmer
Journal: BMJ (1977)

Respiratory side effects of beta-blockers SIR,-I would like to comment on one aspect of the hazards of beta-blockers (leading article, 26 February, p 529)-namely, their use in patients with airways obstruction.It is well known that blockade of beta2 receptors may lead to bronchoconstriction in asthmatics.'This risk is said to be less with the so-called selective beta-blockers, which block predominantely the beta, receptors.My
Vomiting as a Complication of the Heimlich Maneuver
Authors: James P. Orlowski
Journal: JAMA (1987)

THE HEIMLICH maneuver has recently been adopted as the standard treatment for the obstructed airway in children, adolescents, and adults.<sup>1</sup>These same standards and guidelines caution that the Heimlich maneuver should only be used in near-drowning situations when the rescuer suspects that foreign matter is obstructing the airway or the victim does not respond appropriately to mouth-to-mouth ventilation. Heimlich and his colleagues<sup>2-5</sup>have been calling for the maneuver to be the first line of treatment for near-drowning victims, to remove water from the lungs and airways. Others have argued that the routine performance of the maneuver without first demonstrating airway obstruction with foreign matter is a waste of valuable time and might produce complications.<sup>6-9</sup> This case report describes a neardrowning victim whose first step of treatment with the Heimlich maneuver resulted in emesis with aspiration, which complicated what otherwise should have been a routine resuscitation. <h3>Report of</h3>
Death During Jogging
Authors: Thomas J. Bassler
Journal: JAMA (1983)

To the Editor.—  Thompson et al (1982; 247:2535) reviewed 12   and attributed 11 deaths to coronary heart disease (CHD). However, the usual CHD risk factors cannot predict who will die during exercise. Also, the relative risk of vigorous/nonvigorous activity actually goes down as the incidence of CHD goes up. They found that the young (aged 30 to 39 years) had an hourly death rate during jogging 99 times the rate during nonvigorous activity. In the oldest age group (50 to 64 years), the relative risk of jogging dropped to only 5. If these deaths were caused by CHD, one could expect a higher risk in the older populations with the more extensive disease. Such is not the case.  My own forensic experience suggests that most of these exercise-related deaths are poorly explained by the autopsy. All too often, the atheroma are trivial and the term CHD is only
Distribution and properties of Ca2+-ATPase, phytase, and alkaline phosphatase in isolated enterocytes from normal and vitamin D-deficient rats.
Authors: S D Chan, D Atkins
Journal: Gut (1983)

The effects of vitamin D-deficiency and repletion on the distribution and activities of Ca2+-ATPase, phytase, and alkaline phosphatase in intact epithelial cells isolated from different regions of the villi and the crypts of the rat jejunum were studied. Similar distribution patterns of activities were found for the three enzymes. In all cases, the enzyme levels were the highest at the villus tip and gradually declined to low activities in the crypt. The Kms were very different between cells in the crypt base and those at the villus tip, the highest Kms being found in the crypt. The activities of these enzymes were reduced in the entire length of the villus in vitamin D-deficient rats. Recovery of the enzymatic levels was observed on vitamin D repletion, but at different rates. Total recovery of activity of Ca2+-ATPase, phytase, and alkaline phosphatase was observed after 18, 24, and 36 hours, respectively, after a single dose of 6.5 nmol (2.5 micrograms) vitamin D3. Enzymatic activities in the crypt cells were not affected by vitamin D3 treatment. These data suggest that Ca2+-ATPase, phytase, and alkaline phosphatase may be distinct entities, and that their activities in the crypt cells may not be vitamin D-dependent.