tbuckley/cabot-search huggingface dataset:
IT-03 * ADOPTIVE TRANSFER OF IL13R 2-SPECIFIC T CELLS FOR THE TREATMENT OF GLIOBLASTOMA: BUILDING ON CLINICAL ACHIEVEMENTS WITH SECOND-GENERATION CARs
Authors: C. Brown, R. Starr, B. Aguilar, B. Chang, A. Sarkissian, A. Naranjo, W.-C. Chang, M. Jensen, M. D'Apuzzo, M. Barish, B. Badie, S. Forman
Journal: Neuro-Oncology (2014)

The poor prognosis for patients with malignant glioma (MG) is largely attributable to invasive therapy-resistant malignant cells responsible for tumor recurrence. Adoptive immunotherapy with T cells genetically modified to express chimeric antigen receptors (CARs) may be an effective and safe strategy for reducing disease recurrence. Our group has developed a CAR T cell immunotherapy targeting IL13Rα2, a receptor over-expressed by a high percentage of MGs. In two previous phase I clinical trials evaluating first-generation IL13Rα2-CAR T cells, we demonstrated the feasibility of this approach, showing an absence of serious therapy-related side-effects and evidence for transient anti-glioma responses. Building on this experience, we have now developed an optimized CAR T cell product incorporating enhancements in CAR design and T cell engineering, which improve T cell persistence and antitumor potency. These include a second-generation CAR containing the 41BB (CD137) costimulatory signaling domain (IL13BBζ-CAR), and a manufacturing strategy using an enriched central memory T cell (Tcm) population for genetic engineering. In orthotopic IL13Rα2+ MG mouse models, single injection of optimized IL13BBζ-CAR Tcm resulted in robust antitumor activity and significantly improved T cell persistence compared to first-generation IL13Rα2-CAR T cells. We also found that IL13BBζ-CAR T cells administered by intracranial (i.c.) delivery outperformed intravenous delivery in MG xenograft mouse models, and were able to eradicated tumors at the primary tumor site and then traffic to tumors in the contralateral hemisphere, providing evidence for CAR T cell targeting of invasive multi-focal disease. Finally, we demonstrated that the optimized IL13BBζ-CAR Tcm, which recognize IL13Rα2 via a membrane-tethered IL13 ligand mutated at a single site (E13Y), exhibited preferential recognition of IL13Rα2 and decreased recognition of the more ubiquitously expressed IL13Rα1. In summary, these studies support the clinical applicability of this optimized IL13BBζ-CAR Tcm therapeutic product for the treatment of MG.
Increasing Levels of Interleukin (IL)-1Ra and IL-6 During the First 2 Days of Hospitalization in Unstable Angina Are Associated With Increased Risk of In-Hospital Coronary Events
Authors: Luigi M. Biasucci, Giovanna Liuzzo, Giamila Fantuzzi, Giuseppina Caligiuri, Antonio G. Rebuzzi, Francesca Ginnetti, Charles A. Dinarello, Attilio Maseri
Journal: Circulation (1999)

A growing body of evidence suggests a role for inflammation in acute coronary syndromes. The aim of this study was to assess the role of proinflammatory cytokines, their time course, and their association with prognosis in unstable angina.We studied 43 patients aged 62+/-8 years admitted to our coronary care unit for Braunwald class IIIB unstable angina. In each patient, serum levels of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6) (which represent sensitive markers of biologically active IL-1beta and tumor necrosis factor-alpha levels, respectively), and troponin T were measured at entry and 48 hours after admission. Troponin T-positive patients were excluded. Patients were divided a posteriori into 2 groups according to their in-hospital outcome: group 1 comprised 17 patients with an uneventful course, and group 2 comprised 26 patients with a complicated in-hospital course. In group 1, mean IL-1Ra decreased at 48 hours by 12%, and IL-6 diminished at 48 hours by 13%. In group 2, IL-1Ra and IL-6 entry levels were higher than in group 1 and increased respectively by 37% and 57% at 48 hours (P<0.01).These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.
Hackers demand $10m for eight million medical records they are holding "hostage"
Authors: J. Lenzer
Journal: BMJ (2009)

Computer hackers have broken into a US state’s prescription monitoring website and deleted more than eight million medical records, replacing the website’s homepage with a $10m (£6.6m; €7.5m) ransom note.

In return for the ransom money the hackers said they would “gladly send along the password” to allow officials to restore the records.

The intrusion into the Virginia website, which is used by pharmacists to track prescription information for certain classes of drugs such as sleeping pills and painkillers, was discovered on 30 April. The website has been removed.

The electronic attack is similar to a case in October 2008 in which hackers …
Stress Hyperglycemia, Inflammation, and Cardiovascular Events
Authors: Katherine Esposito, Raffaele Marfella, Dario Giugliano
Journal: Diabetes Care (2003)

One-third of all individuals with hyperglycemia admitted to an urban general hospital do not have a previous diagnosis of diabetes; in these patients, hyperglycemia is a risk factor for adverse outcomes during acute illness (1). For example, in patients presenting with acute myocardial infarction, glucose values in excess of 6.1–8.0 mmol/l were associated with a threefold increase in mortality and a higher risk of heart failure (2). Control of hyperglycemia with intensive insulin therapy during acute illness results in marked improvements of clinical outcomes (3).

Dandona et al. (4) put forward a working hypothesis linking in a feedback loop of glucose (and …
Patterns of Expenditures and Use of Services Among Older Adults With Diabetes: Implications for the transition to capitated managed care
Authors: Julie S Krop, Neil R Powe, Wendy E Weller, Thomas J Shaffer, Christopher D Saudek, Gerard F Anderson
Journal: Diabetes Care (1998)

OBJECTIVE To examine health care use and expenditures among older adults with diabetes, investigate factors that are associated with higher expenditures, and describe the policy implications of caring for this population under managed care. RESEARCH DESIGN AND METHODS A cross-sectional analysis of expenditures for individuals with diabetes over age 65 years from a nationwide 5% random sample of Medicare beneficiaries was conducted during 1992. All components of medical care covered under Medicare were examined. Multivariate analysis was used to assess the contribution of age, race, sex, number of diabetic complications, and comorbidity (Charlson Index) on total expenditures. RESULTS On average, individuals with diabetes (n = 188,470) were 1.5 times (P &amp;lt; 0.0001) as expensive as all Medicare beneficiaries (n = 1,371,960). However, there were wide variations, with the most expensive 10% of beneficiaries with diabetes accounting for 56% of expenditures for individuals with diabetes and the least expensive 50% accounting for 4% Acute carehospitalizations accounted for the majority (60%) of total expenditures, whereas outpatient and physician services accounted for 7 and 33%, respectively. There were no differences in the number of complications for all older adults with diabetes compared with those with the highest expenditures. However, the average number of hospitalizations was 1.6 times (0.53 vs. 0.34; P &amp;lt; 0.0001) higher, and the average length of stay was 2 days longer, among older adults with diabetes (P &amp;lt; 0.0001). In the regression model, age and male sex (factors currently used to set payment rates for Medicare managed care enrollees), and number of diabetic complications, but not race, were positively related to expenditures, yet had minimal predictive power (R2 = 0.0006). The addition of the Charlson Index, also positively related to expenditures, was able to explain up to 20% of the variation in total expenditures (R2 = 0.196). CONCLUSIONS There are large variations in expenditures among older adults with diabetes. Because elderly beneficiaries with diabetes are more expensive than the average older adult, current Medicare capitation rates may be inadequate. To avoid selection bias and undertreatment of this vulnerable population under managed care, methods to construct fair payment rates and safeguard quality of care are desirable.
Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity?
Authors: Alexandra Traverse-Glehen, Lucile Baseggio, Evelyne Callet- Bauchu, Dominique Morel, Sophie Gazzo, Martine Ffrench, Aurélie Verney, Delphine Rolland, Catherine Thieblemont, Jean-Pierre Magaud, Gilles Salles, Bertrand Coiffier, Françoise Berger, Pascale Felman
Journal: Blood (2007)
Radon exposures in a Jerusalem public school.
Authors: E D Richter, E Neeman, I Fischer, M Berdugo, J B Westin, J Kleinstern, M Margaliot
Journal: Environmental Health Perspectives (1997)

In December 1995, ambient radon levels exceeding 10,000 Bq/m3 were measured in a basement shelter workroom of a multilevel East Talpiot, Jerusalem, public elementary school (six grades, 600 students). The measurements were taken after cancers (breast and multiple myeloma) were diagnosed in two workers who spent their workdays in basement rooms. The school was located on a hill that geologic maps show to be rich in phosphate deposits, which are a recognized source for radon gas and its daughter products. Levels exceeding 1000,000 Bq/m3 were measured at the mouth of a pipe in the basement shelter workroom, the major point of radon entry. The school was closed and charcoal and electret ion chamber detectors were used to carry out repeated 5-day measurements in all rooms in the multilevel building over a period of several months. Radon concentrations were generally higher in rooms in the four levels of the building that were below ground level. There were some ground-level rooms in the building in which levels reached up to 1300 Bq/m3. In rooms above ground level, however, peak levels did not exceed 300 Bq/m3. Exposure control based on sealing and positive pressure ventilation was inadequate. These findings suggested that radon diffused from highly contaminated basement and ground-floor rooms to other areas of the building and that sealing off the source may have led to reaccumulation of radon beneath the building. Later, subslab venting of below-ground radon pockets to the outside air was followed by more sustained reductions in indoor radon levels to levels below 75 Bq/m3. Even so, radon accumulated in certain rooms when the building was closed. This sentinel episode called attention to the need for a national radon policy requiring threshold exposure levels for response and control. A uniform nationwide standard for school buildings below 75 Bq/m3 level was suggested after considering prudent avoidance, the controversies over risk assessment of prolonged low-level exposures in children, and the fact that exposures in most locations in the Talpiot school could be reduced below this level. Proposal of this stringent standard stimulated the search for a strategy of risk control and management based on control at the source. This strategy was more effective and probably more cost effective than one based on suppression of exposure based on sealing and ventilation. Because many Israeli areas and much of the West Bank area of the Palestinian National Authority sit on the same phosphate deposits, regional joint projects for surveillance and control may be indicated.
EXTENSIVE CUT-THROAT WITH COMPLETE LACERATION OF TRACHEA AND ESOPHAGUS
Authors: G. D. Scott
Journal: JAMA (1928)

While many cases are reported of extensive laceration of the important structures in the neck, such as complete severence of the larynx, trachea and larger muscles, yet after an extensive search of the literature I have not found recorded a case of complete severence of both esophagus and trachea. It is for this reason that this case of complete severence of both trachea and esophagus is here reported. Cathcart<sup>1</sup>reported a severe cut-throat in which the structures had been divided above the level of the hyoid bone down to the vertebral column. The main vessels were not cut, but one or both lingual and possibly the facial arteries had been divided. Tracheotomy was performed and two days afterward the parts were drawn together with mattress sutures of silkworm gut. The edges of the wound, however, became greatly inflamed and sloughed and the stitches had to be taken out. A fetid
Abstract 5569: DNA methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with acute myeloid leukemia
Authors: Maribel Tirado-Gomez, Sharon Fonseca, Cristina Munoz, Paul Cordero, Raul Bernabe, Mercedes Lacourt, Noridza Rivera, Maribel Cotto, Eddiemar Ortiz, Mirelis Acosta
Journal: Cancer Research (2012)

Abstract Background: DNA methylation of gene promoters have been show to play a role in the pathogenesis of acute myeloid leukemia (AML). We present in this study a preliminary report of the methylation status of MLH1, p16, SOCS1, ER and CDH1 in Puerto Rican patients with AML. Methods: Peripheral blood was obtained from 24 patients with diagnosis of acute myeloid leukemia before and after their induction treatments. DNA was isolated and further modified with sodium bisulfite. Methylation-specific polymerase (MSP) chain reaction was performed to detect aberrant promoter methylation of MLH1, p16, SOCS1, ER and CDH1. Results: Samples from a total of 24 patients were analyzed. The mean age was 47 years (range 22-70) with 21/24 patients younger than 60 years (88%). Most of the patients were female (13/24, 54%). Ten patients had diploid cytogenetics (42%), 4 had low risk cytogenetics (17%) and 10 had high risk cytogenetics (42%). Nineteen patients were de Novo AML (79%). Sixteen patients (67%) presented with WBC counts higher than 10 x 109/L. Seventeen patients (71%) achieved a complete response at the end of the induction therapy. Frequencies of gene methylation before treatment were as follows: MLH: 3/24 (13%); p16: 6/24 (25%); SOCS1:13/24 (54%); ER: 16/24 (67%) and CDH1: 4/24 (16.7%). Conclusions: No correlation between methylation status of p16 and MLH1 before treatment and clinicopathological characteristics was noted. Unmethylated CDH1 was more common among the novo AML patients. Methylation of SOCS1 was more common among patients that achieve a CR after induction therapy. This sample is a small one, so any correlation must be further tested in a more ample sample. Collection of more patient's samples and correlation with clinical data and patient's ultimate outcome is ongoing. 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 5569. doi:1538-7445.AM2012-5569
A CASE OF SYSTEMIC BLASTOMYCOSIS, WITH BLASTOMYCETES IN THE SPUTUM.
Authors: DANIEL N. EISENDRATH
Journal: JAMA (1905)

Through the efforts of Drs. James Nevins Hyde and Frank Hugh Montgomery and other observers, cutaneous blastomycosis is now generally recognized as an entity. The number of reported cases of systemic blastomycosis being few, it seems justifiable to report more or less fully new cases as they occur, so that by a study of the entire group it will be possible definitely to place the disorder in its proper position in medicine. There are now on record four cases of systemic blastomycosis, in which the causative organism appears identical. These were recorded by Busse and Buschke,<sup>1</sup>Montgomery and Walker,<sup>2</sup>Ormsby and Miller<sup>3</sup>and Cleary.<sup>4</sup>Three of the cases were in Chicago, and two of these occurred in the practice of Drs. Hyde and Montgomery. Another case which closely conforms, and which by some observers is classed here, was that reported by Ophüls and Moffitt<sup>5</sup>of
Introduction of B-chain-inactivated ricin into mouse macrophages and rat Kupffer cells via their membrane Fc receptors.
Authors: K Refsnes, A C Munthe-Kaas
Journal: The Journal of Experimental Medicine (1976)

Experiments have been made to test whether the toxic lectin ricin can be bound to and introduced into cells by some other mechanism than via its B chain, the natural binding moiety of the toxin, without its toxic effect being neutralized. Complexes consisting of ricin and antibodies specifically directed against ricin B chain were incubated with mouse peritoneal macrophages and rat Kupffer cells, which are known to possess surface receptors for the Fc portion of the immunoglobulin molecule. After incubation for 26 h, cellular protein synthesis, as measured by incorporation of labeled leucine into acid-insoluble material, was completely inhibited. HeLa cells, which do not possess Fc receptors, were unaffected by the complex. The effect of the complex on protein synthesis of macrophages was prevented by soluble antigen-antibody complexes, but not by the presence of lactose which prevents attachment of the ricin B chain to the cell membrane. The [ricin-antiricin B] complex was attached to red cells, and the resulting complex was incubated with rat Kupffer cells. Cellular protein synthesis ceased after 6 h, and phase contrast microscopy studies showed that the complexes were taken up by the Kupffer cells. The data indicate that ricin, when present in the complex with antiricin B, can be introduced into cells through cell membrane receptors other than the B chain receptor, in this case the Fc receptor, and that the internalized toxin retains a least part of its activity.
Pancreatic Cancer in Mice and Man: The Penn Workshop 2004
Authors: Ralph H. Hruban, Anil K. Rustgi, Teresa A. Brentnall, Margaret A. Tempero, Christopher V. Wright, David A. Tuveson
Journal: Cancer Research (2006)

Abstract A three-day conference cosponsored by the National Cancer Institute Mouse Models of Human Cancer Consortium and the Abramson Cancer Center of the University of Pennsylvania was convened on December 1, 2004, in Philadelphia, Pennsylvania. The purpose of the conference was to compare the histopathologic changes in murine models of exocrine pancreatic cancer to human disease and to discuss potential preclinical applications of these models. The participants of this international meeting included over 100 physicians and scientists with expertise in pancreatic cancer pathology, therapy, detection, and biology, and they were organized accordingly into working groups. The format of the meeting was a series of short presentations by individual participants followed by working group breakout sessions. The working groups presented their reports on the final day of the conference, and highlights of selected individual presentations and working group recommendations are summarized here and in an accompanying pathology consensus report. (Cancer Res 2006; 66(1): 14-7)
Symptomatic treatment of primary pneumatosis coli with metronidazole.
Authors: B W Ellis
Journal: BMJ (1980)

fistula without induration.His complaints had disappeared.Three months after operation he had an elective proctocolectomy.At laparotomy not only a gastrocolic but also an ileosigmoid fistula was found.Both fistulas and the entire colon and rectum were removed via the intersphincteric approach for removal of the rectum, though severe rectal inflammation made the procedure difficult.The gastrocolic fistula was also resected, and the patient made an uncomplicated recovery, gaining 30 kg; the perineal wound has healed completely.
The Scope of False-Positive lodine-131 Images for Thyroid Carcinoma
Authors: DANIEL P. GREENLER, HERBERT A. KLEIN
Journal: Clinical Nuclear Medicine (1989)

Iodine-131 is used to detect and treat functioning lesions of papillary and follicular carcinoma of the thyroid. False-positive images although rare, do occur, with major categories being 1) body secretions, 2) pathologic transudates and inflammation, 3) nonspecific mediastinal uptake, and 4) neoplasms of nonthyroidal origin. The authors present eight cases that fall into the first three categories, including three types not previously reported--a lymphoepithelial cyst, a scrotal hydrocele, and a skin burn. The classification of mediastinal uptake as false positive is tentative. High-dose images and those exploiting therapeutic doses have an increased detection rate for both true and spurious lesions. Appropriate caution is advised in the interpretation of I-131 images.
436 ACUTE HEPATITIS C IN PERSONS INFECTED WITH THE HUMAN IMMUNODEFICIENCY VIRUS (HIV): THE “REAL-LIFE SETTING” PROVES THE CONCEPT
Authors: P. Ingiliz, M. Obemeier, L. Weitner, C. Cordes, A. Moll, B. Hintsche, F. Schlote, S. Koeppe, S. Christensen, C. Mayr, A. Baumgarten
Journal: Journal of Hepatology (2011)
The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes.
Authors: L E Waspe, C P Ordahl, P C Simpson
Journal: Journal of Clinical Investigation (1990)

Cardiac hypertrophy produced in vivo by pressure overload is characterized by selective up-regulation of the fetal/neonatal beta-cardiac myosin heavy chain (MHC) isogene. However, a molecular signal for beta-MHC isogene induction has not been identified. We examined cardiac MHC isogene expression in a cell culture model for hypertrophy. alpha-MHC and beta-MHC iso-protein and iso-mRNA levels in cultured cardiac myocytes were quantified during hypertrophy stimulated by the alpha 1-adrenergic agonist, norepinephrine (NE). beta-MHC iso-protein content was increased 3.2-fold vs. control (P less than 0.001), whereas alpha-MHC isoprotein content was not changed significantly (1.4-fold vs. control, P = NS). MHC iso-mRNA levels were quantified by nuclease S1 analysis, using a single oligonucleotide probe. NE increased beta-MHC iso-mRNA content by 3.9-fold vs. control (P less than 0.001), but there was no change in alpha-MHC iso-mRNA (1.1-fold vs. control, P = NS). The NE-stimulated increase in beta-MHC iso-mRNA preceded in time the increase in beta-MHC isoprotein accumulation. The EC50 for NE induction of beta-MHC was 40 nM, and pharmacologic experiments indicated alpha 1-adrenergic receptor specificity. alpha-MHC isogene expression was predominant in control myocytes (68% alpha-isoprotein and 60% alpha-iso-mRNA). In contrast, beta-MHC expression was equal to alpha-MHC or predominant after treatment with NE (51% beta-isoprotein and 69% beta-iso-mRNA). Thus, alpha 1-adrenergic receptor stimulation increases the cellular contents of beta-MHC iso-mRNA and beta-MHC isoprotein during hypertrophy of cultured neonatal rat cardiac myocytes, but does not change the levels of alpha-MHC iso-mRNA or isoprotein. The effect on beta-MHC is mediated primarily at the level of mRNA steady-state level (pretranslational). Activation of the alpha 1-adrenergic receptor is the first identified molecular signal for increased beta-MHC isogene expression in a model of cardiac hypertrophy.
Pocket-creation method of endoscopic submucosal dissection to achieve en bloc resection of giant colorectal subpedunculated neoplastic lesions
Authors: Yoshikazu Hayashi, Keijiro Sunada, Haruo Takahashi, Hakuei Shinhata, Alan Lefor, Akira Tanaka, Hironori Yamamoto
Journal: Endoscopy (2014)

Endoscopic submucosal dissection (ESD) has become a standard minimally invasive therapy in Japan for large, superficial, colorectal neoplasms [1]. Although polypectomy or endoscopic mucosal resection is generally effective for polypoid lesions, ESD is an effective alternative to achieve en bloc resection in difficult cases, such as giant, subpedunculated, neoplastic lesions that are at least 3 cm in diameter [2]. However, ESD for giant, subpedunculated, neoplastic lesions is associated with technical difficulties because severe submucosal fibrosis occurs at the center of these lesions due to prolapse, resulting in the muscle layer being pulled upward.