tbuckley/cabot-search huggingface dataset:
Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM
Authors: Benjamin Beck, G Yancey Gillespie, Richard D. Lopez, Gretchen A. Cloud, Cathy Langford, Hyung Kim, Lualhati Harkins, Lawrence S. Lamb
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) remains frustratingly impervious to any existing therapy. We have previously shown that GBM is sensitive to recognition and lysis by ex vivo activated γδ T cells, a minor subset of lymphocytes that innately recognize autologous stress-associated target antigens via the T cell receptor and/or NKG2D. However, circulating γδ T cell counts and function are significantly reduced in patients with GBM. We sought to determine the role of γδ T cells in the immune response to high-grade gliomas in C57BL/6 mice bearing GL261 cell line-derived intracranial gliomas. Examination of mice 15 days after intracranial tumor placement and prior to development of neurologic symptoms revealed small infiltrating high-grade gliomas near the injection site. Concurrently, the peripheral blood γδ T cell count was significantly increased when compared to control mice that received only the methylcellulose vehicle (p=0.0003). T cell expansion was confined to the γδ T cell compartment, and a substantial proportion of γδ T cells in tumor-bearing mice expressed Annexin-V (20%-45%) indicating progression to apoptosis. Annexin-V expression in control mice was confined to 2-5% of γδ T cells, significantly less than tumor-bearing mice (p&amp;lt;0.0001). GL261-derived tumors expressed γδ T cell target stress-associated NKG2D ligands H60, MULT-1 and RAE-1, yet γδ T cells did not infiltrate the intracranial tumors. In a separate experiment, we found no survival advantage between wild-type (WT) mice over γδ T cell-deficient (C57BL/6α-/−) tumor-bearing mice. Based on this observation that activated γδ T cells did not invade the tumor, we treated mice with a stereotactic intracranial injection of 1.5 x 106 ex vivo expanded/activated γδ T cells approximately 15 minutes following placement of 5 x 106 GL261 glioma cells. Mice that received intracranial γδ T cells were protected from tumor development at site of injection, although distant tumors did eventually form. These data suggest that γδ T cells are stimulated in glioma-bearing mice and that depletion in γδ T cells observed in mouse glioma models and human GBM are likely due to activation-induced cell death in response to the tumor. Activated γδ T cells do not traffic to the tumor parenchyma; however, an antitumor effect can be achieved by direct placement of ex vivo activated γδ T cells in the vicinity of microscopic disease, suggesting a potential post-resection strategy for treatment of minimal residual GBM. 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 530. doi:1538-7445.AM2012-530
Pain in Sickle Cell Disease
Authors: Orah S. Platt, Bruce D. Thorington, Donald J. Brambilla, Paul F. Milner, Wendell F. Rosse, Elliott Vichinsky, Thomas R. Kinney
Journal: New England Journal of Medicine (1991)

Acute episodes of pain are the principal symptom of sickle cell disease, but little is known about the epidemiologic features of these episodes or risk factors for them, nor is it known whether patients with high rates of such episodes die prematurely. We prospectively studied the natural history of sickle cell disease in 3578 patients ranging from newborns to persons up to 66 years old who were followed at clinical centers across the United States.
Modifiable neuronal connections: an overview for psychiatrists
Authors: K J Jeffery, I C Reid
Journal: American Journal of Psychiatry (1997)

Synaptic plasticity is currently the target of much neurobiological research, because it is thought to play an important role in brain function (particularly memory formation).However, it has attracted little attention from psychiatrists to date despite accumulating evidence that links it to various clinical syndromes, including amnesia and possibly psychosis.The purpose of this article is to present an overview of the two major arms of synaptic plasticity research-theoretical (the field of neural network modeling) and neurobiological (long-term potentiation).Artificial neural networks are a class of theoretical model that has been developed with the aim of understanding how information could, in principle, be represented by large numbers of interconnected and relatively simple units.Over the past few decades, several theoretical accounts of information-processing mechanisms have been developed, and these are briefly reviewed.The principle common to representation formation in nearly all neural networks is that of "associability"-the idea that streams of information are combined by forming, strengthening, or pruning connections between them to form new representations that can later be retrieved.Associability also lies at the heart of psychological theories of information storage in the brain.Research into associability has directed the attention of many experimenters toward the possible biological correlates of such mechanisms.Of particular interest is the recent discovery that some neurons appear to possess connections of modifiable strength.The implications of this finding for psychiatry are discussed in relation to representational disorders such as delusions and amnesia.
Incidence of Megaloblastic Anemia after Total Gastrectomy
Authors: Lloyd D. MacLean, R. Dorothy Sundberg
Journal: New England Journal of Medicine (1956)

THE investigations of Castle and co-workers1 2 3 4 5 6 over the past quarter century strongly support the thesis that pernicious anemia is the result of a gastric defect manifested by an inadequate production of intrinsic factor, which is responsible for absorption of extrinsic factor, or vitamin B12, from the gastrointestinal tract. If pernicious anemia is not a more complex deficit than a lack of intrinsic factor and if the stomach is the only source of this material, one would expect pernicious anemia to develop invariably after total gastrectomy. Studies utilizing the fecal or urinary excretion of radioactive vitamin B12 as . . .
Abstract P4-04-08: A Potential non-viral vector to transfect dendritic cell and thereby MHC-Class I antigen presentation might be a potential use in carcinoma
Authors: S Shaheen, H Akita, I Souichirou, N Miura, H Harashima
Journal: Cancer Research (2012)

Abstract To date almost no remarkable potential non-viral vector was developed to transfect promisingly primary dendritic cell like Bone Marrow Derived Dendritic Cell (BMDC) so that it might generate antigen presentation while epitopic-plasmid was delivered. Here we have introduced a potential non-viral vector named Stearyl-KALA MEND (100–130 nm, zeta potential 35–40 mV), which expressed to date the highest transgene expression while firefly luciferase was introduced (sub-cloned), and thereby promising antigen presentation in vitro while OVA plasmid containing MHC Class-I restricted SIINFEKL epitope was introduced and co-cultured with B3Z T-cell hybridoma. On the basis of these results, we used this vector to transfect BMDC and harvested the DC to chase the corresponding EG7-OVA induced tumor ex vivo. Later we further immunized mice directly with STR-KALA MEND containing OVA plasmid and challenged against the tumor (EG7-OVA induced). In this in vivo study we found also a significant antitumor activity. To evaluate the promptness of our vector we further sub-cloned Mart-1 gene, in our sub-cloned plasmid vector and immunized the mice as before. Thereafter inserting B16F10 melanoma cells to the immunized mice we found also a significant antitumor activity after 24 days of inoculation. Thus the vector, STR-KALA MEND might be a future potential use as DNA vaccine in anti-tumor methodology. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-08.
Tube Feeding Increases the Gastric-Emptying Rate Determined by Gastroesophageal Scintigraphy
Authors: Wengen Chen, Ion Codreanu, Jigang Yang, Geming Li, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2013)

The aim of this study was to determine whether tube feeding affects the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients.Gastroesophageal reflux scintigraphy studies of 700 pediatric patients aged 1 week to 16 years were retrospectively analyzed. From these, 350 subjects received their study meal via a feeding tube, and 350 subjects received their meal as oral feeding. Gastric-emptying rate at 60 minutes was calculated, and the results compared. Stratification analysis for age, sex, and type and volume of administered meal was also performed.The average rate of the gastric emptying was higher in the tube feeding compared with oral feeding group (52.9% ± 17.9% vs 44.2% ± 15.1% gastric emptying at 1 hour, P < 0.01). The prevalence of fast gastric emptying, defined as greater than 50% emptying at 60 minutes, was also higher in the tube feeding group, being registered in 59.7% (209/350 cases) versus only 31.4% (110/350 cases) in the oral feeding group, P < 0.01. The difference persisted following stratification analysis for sex, age, and type and volume of ingested meal.Our findings show that tube feeding increases the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients. The effect proved independent on such factors as sex, age, and type or volume of ingested meal.
FRI0479 Comparison of low field mri inflammatory findings on the hand in patients with rheumatoid arthritis and systemic sclerosis
Authors: B. N. Stamenkovic, A. M. Stankovic, D. Menkovic, A. N. Dimic, J. M. Nedovic, S. K. Stojanovic, S. B. Milenkovic, N. Damjanov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Qualitative MRI assessment of hand inflammation in scleroderma (SSc) has been reported in only few MRI studies. However, there are no studies with quantitative assessment and differentiation of arthritis in SSc from other arthritides <h3>Objectives</h3> To compare low field MRI features- synovitis, bone marrow oedema (BME) and bone erosions, among patients with inflammatory hand pain in rheumatoid arthritis (RA) and systemic sclerosis (SSc). <h3>Methods</h3> 35 RA (EULAR/ACR 2010 criteria) and 82 SSc pts with clinical involvement of hand joints were consecutively included in the study. The 0.2T extremity contrast MRI was performed on the wrist and MCP joints of the more painful hand in all the pts. The inflammatory changes (synovitis, BME and bone erosions) were scored by two independent musculoskeletal radiologists who followed the recommendations of the OMERACT RAMRIS. Total scores were compared between SSc and RA groups of patients. <h3>Results</h3> 35 RA pts (mean age 54.3) and 82 SSc patients (mean age 54.5) with painful hands underwent 0.2T extremity MRI. Rheumatoid factor (RF) and anti-ciltrullinated protein antibodies (ACPA) were found in 74.3% and 89% RA pts, respectively, and in 14.6% and 13.4% SSc pts. Higher frequency of synovitis with statistically higher MRI score was observed in RA compared to SSc pts (wrist: 4.37±1.31 vs. 2.69±2.29, p&lt;0.001; MCP joints: 5.26±2.09 vs. 3.15±2.95, p&lt;0.001). MRI erosions scored on the wrist and MCP joints were statistically higher in RA pts compared to SSc pts (wrist: 20.57±10.23 vs. 6.58±10.89, p&lt;0,001; MCP joints: 10.51±7.90 vs. 3.99±9.82, p&lt;0.001). MRI BME scores were, also, statistically higher in RA pts compared to SSc on the wrist (18.60±5.01 vs. 6.84±7.43, p&lt;0.001) and on MCP joints (9.09±4.27 vs. 4.04±4.76, p&lt;0.001) <h3>Conclusions</h3> Our results suggest that painful hand in RA and SSc pts is associated with inflammatory changes on MRI: synovitis, erosions and bone marrow oedema. MRI scores of inflammation are much higher in RA than in SSc pts. MRI might help the physician to differentiate RA and SSc in pts with painful hand. <h3>Disclosure of Interest</h3> None Declared
Nearly 3,000 Randomized in North American Prevention Trial
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Nearly 3,000 Randomized in North American Prevention Trial Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 20, 21 October 1992, Page 1555, https://doi.org/10.1093/jnci/84.20.1555-a Published: 21 October 1992
Abstract 2760: Gemcitabine induced lytic EBV replication and confers ganciclovir susceptibility to EBV-positive gastric cancer
Authors: Hyemi Kim, Hyun Gyu Lee, Jeon Han Park, Jae Myun Lee
Journal: Cancer Research (2012)

Abstract Epstein-Barr virus (EBV) is a dsDNA human gamma herpes virus which infects more than 90% of human populations. It is associated with the development of malignancies such as Burkitt's lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Gastric cancer is the second most common cancer in the world and the highest incidence is in Korea. The constant presence of the viral genome in EBV associated gastric cancer tissue offers the potential for novel EBV targeted therapies using antiviral nucleoside drug. Ganciclovir (GCV) is the drug of choice in herpes virus infection, however, GCV alone have been unsuccessful in the treatment of EBV associated malignancies because the virus maintains a latent state of replication in tumor, and thymidine kinase (BXLF1) and protein transferase (BGLF4), express only during lytic state of replication. In recent years, novel treatment strategies are being investigated where in lytic replication of the virus in EBV associated cancer is induced prior to the use of GCV. We investigate Gemcitabine (Gem), which is one of newly discovered potential lytic inducers found from FDA approved drug library screen using BZLF1 promoter reporter system. We examined whether the combination of GCV and Gem is more effective than Gem alone for killing EBV-positive gastric cancer cells. We found GCV significantly enhanced the ability of Gem to kill EBV-positive, but not EBV negative, gastric carcinoma cells in vitro. Also we found that low dose (2.5ng/ml) and short term exposures (24hr) of the EBV positive gastric cancer cell line SNU719 to Gem induced expression of the EBV lytic phase proteins. Viral kinases were also induced by short term and low dose exposure. Short term and low dose exposure to Gem in combination with GCV induced tumor cell death and cell proliferation inhibition. In conclusion, pharmacologic induction of the lytic viral kinases in tumor cells using Gem, followed by treatment with GCV is useful in EBV associated gastric cancer in vitro. And this virus-targeted antitumor strategy may provide a new therapeutic approach to EBV-associated gastric cancer. 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 2760. doi:1538-7445.AM2012-2760
A VA Exit Strategy
Authors: William B. Weeks, David Auerbach
Journal: New England Journal of Medicine (2014)

Interview with Prof. William Weeks on a proposal for shifting VA’s health care role to benefits and coordination. (10:44)Download It may be time for the Veterans Health Administration to transition out of the health care delivery business, instead supporting utilization of private-sector health care by subsidizing coverage for enrolled veterans and coordinating care for its service population.
No End to Uncertainty about Inhaled Glucocorticoids in Preterm Infants
Authors: Barbara Schmidt
Journal: New England Journal of Medicine (2015)

Bronchopulmonary dysplasia, a chronic neonatal lung disease, affects at least 10,000 preterm infants in the United States each year. It is caused by acute lung injury due to surfactant insufficiency, artificial ventilation, the use of supplemental oxygen, and inflammation, followed by abnormal repair and impaired lung growth.1 Bronchopulmonary dysplasia is the single most common complication that occurs in extremely preterm infants (those who are born at <28 weeks of gestation) or extremely-low-birth-weight infants (those who weigh <1000 g at birth) during their initial hospitalization.1 This respiratory complication, which is typically diagnosed at a postmenstrual age of 36 weeks, is defined . . .
THU0364 Longterm follow-up for patients MIT retroperitnoeal fibrosis after medical and surgical treatment
Authors: H. Cash, C. Noack, T.F. Fuller, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

Background Retroperitoneal fibrosis (RPF) is rare disease wich presents with bilateral hydronephrosis as the most common symptom. Objectives One of the aims in the treatment of retroperitoneal fibrosis (RPF) is to restore renal drainage and maintain renal function. We investigated the rate of ureteral stent-freedom after conservative and surgical therapy Methods Patient data was retrospectively analyzed. For primary diagnostics CT or MRI imaging was used as well as for treatment monitoring. Results Between 1995 and 2010 33 patient (21men; 12 women) were treated for RPF at our institution. The median follow-up was 55 months, the median age 60y. In addition to imaging studies 15 pat. were biopsied for diagnosis. 29 patients received immunosuppressive therapy, in 16 (66%) cases as combination therapy. 25 pat. presented with hydronephrosis at time of the primary diagnosis. Overall for 40 renal units ureteral stenting was necessary. After initiation of the medical treatment 22 (76%) patients showed a stable disease or disease regression in follow-up imaging. In 7 cases an addiditional laparoscopic urerolysis was performed. After 6 months 7 (18%) renal units were stent-free. Until the end of 2011 another 10 renal units became stent-free, with a median time to stent freedom of 22 months. Of the patient with an ureterolysis 4 patients were stent-free after 12 months. Three patients had to receive nephrectomy 55 months (mean) after the initiation of the immunosuppression. At the end-point of our analysis the median creatinin-level was 1.05mg/dl, 3 patients needing dialysis. Conclusions The medical treatment of RFP was complex and lead to freedom of ureteral stenting in 39% of cases only. If a surgical treatment at an earlier stage leads to superior stent-free rates remains to be further elucidated. Disclosure of Interest None Declared
Abstract 1061: Glutathione S-transferase P1 is required for growth and survival of human glioma cells
Authors: Francis Ali-Osman, Jiewu Liu
Journal: Cancer Research (2010)

Abstract Overexpression of glutathione S-transferase p1 (GSTP1), a protein involved in Phase II metabolism and cell signaling, is a hallmark of diverse human malignancies, including gliomas, and is associated with resistance to therapy, aggressive tumor growth and poor patient survival. Although, the function of GSTP1 in drug metabolism and detoxification is well documented, its role in regulating tumor cell growth remains unclear. Here, we report that in human glioma characterized by high GSTP1 expression, GSTP1 is obligately required for the growth and survival of the tumor cells. For this, we stably infected cells of the MGR3 glioblastoma multiforme (GBM) cell line that expresses high de novo levels of GSTP1, with a lentiviral vector that either expresses a short hairpin RNA (shRNA) specifically targeting to GSTP1 or a control shRNA. We isolated two clones, 1 and 2 and showed by western blotting that the GSTP1 specific shRNA mediated decreases in GSTP1 expression of 92% and 100%, respectively, relative to controls while infected with eGFP shRNA. Growth kinetic analysis showed the in vitro growth rates of both clones 1 and 2 to be significantly lower than that of the parental or control clone, with population doubling times of 108.9 ± 17.6 hr for clone 1 and 94.8 ± 4.3 hr for clone 2, compared with 40.6 ± 2.6 hr for the parental cells and 44.7 ± 2.0 hr for the control transfected cells. Cell cycle analysis showed that the GSTP1 knockdown induced a significant almost 2-fold increase in the sub-G1 (apoptotic) population that correlated with an increase in caspase 3/7 activation. Western blotting showed no significant changes in total protein levels of ERK, JNK and p38 MAPK following GSTP1 knockdown, however, phosphorylation levels of both ERK1/2 and JNK1/2 increased significantly, while phospho- p38 MAPK levels did not change. JNK downstream signaling, viz., phosphorylation of c-Jun, increased dramatically in cells of the two clones. These alterations in MAPK signaling in the tumor cells associated with GSTP1 silencing correlated with the decreased survival and growth kinetics and corresponding changes in apoptosis/survival signals, including, decreased bcl2 and increased bax levels in the tumors. Our results show that GSTP1 is required for cell survival and growth of human GBM cells that naturally over-express high GSTP1 levels. This is consistent with the aggressive tumor growth and poor survival of patients whose tumors contain high levels of GSTP1 and provide a rationale for targeting GSTP1 as a potential therapeutic strategy for malignant gliomas. Supported by grants RO1CA112519, RO1CA127872, RO1CA91438, P30CA114236 and P5OCA108786 from the National Institutes of Health (USA). 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 1061.
Flavone-8-Acetic Acid and the Natural Flavonoids
Authors: M. RABINOVITZ
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Flavone-8-Acetic Acid and the Natural Flavonoids Get access MARCO RABINOVITZ MARCO RABINOVITZ Laboratory of Biological Chemistry National Cancer InstituteBldg. 37, Rm. 5D-02 Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 12, 21 June 1989, Page 962, https://doi.org/10.1093/jnci/81.12.962 Published: 21 June 1989
META-ANALYSIS OF RANDOMIZED CONTROL TRIALS (RCTS) COMPARING PERCUTANEOUS LEFT ATRIAL APPENDAGE (WATCHMAN DEVICE) CLOSURE VERSUS ADJUSTED DOSE WARFARIN FOR STROKE PROPHYLAXIS IN NON-VALVULAR ATRIAL FIBRILLATION
Authors: Navkaranbir S. Bajaj, Saurabh Gaba, Pankaj Arora, Mustafa Ahmed, Rajat Kalra, Takumi Yamada, Oluseun Alli, Navin Nanda, Navin Nanda
Journal: Journal of the American College of Cardiology (2015)