tbuckley/cabot-search huggingface dataset:
Glycogen synthase kinase 3 beta: can it be a target for oral cancer
Authors: Rajakishore Mishra
Journal: Molecular Cancer (2010)

Despite progress in treatment approaches for oral cancer, there has been only modest improvement in patient outcomes in the past three decades. The frequent treatment failure is due to the failure to control tumor recurrence and metastasis. These failures suggest that new targets should be identified to reverse oral epithelial dysplastic lesions. Recent developments suggest an active role of glycogen synthase kinase 3 beta (GSK3 β) in various human cancers either as a tumor suppressor or as a tumor promoter. GSK3β is a Ser/Thr protein kinase, and there is emerging evidence that it is a tumor suppressor in oral cancer. The evidence suggests a link between key players in oral cancer that control transcription, accelerated cell cycle progression, activation of invasion/metastasis and anti-apoptosis, and regulation of these factors by GSK3β. Moreover, the major upstream kinases of GSK3β and their oncogenic activation by several etiological agents of oral cancer support this hypothesis. In spite of all this evidence, a detailed analysis of the role of GSK3β in oral cancer and of its therapeutic potential has yet to be conducted by the scientific community. The focus of this review is to discuss the multitude of roles of GSK3β, its possible role in controlling different oncogenic events and how it can be targeted in oral cancer.
Are Heroes Obsolete?
Authors: R. Dale Liechty
Journal: JAMA (1979)

HAVE great ideas become obsolete? Take the ancient concept of good and evil, for example: the recurrent theme of the Bible, Dante, Milton, Dostoevski, Melville, Faulkner, and Solzhenitzyn. Has our technological existence left any room for their stories of "the human heart in conflict with itself"? Malcolm Muggeridge, the urbane former editor of<i>Punch</i>, appearing on William Buckley's "Firing Line," put it this way: "When I bring up the subject of Good and Evil, my audiences don't even know what I'm talking about." Some popular philosophies simply dismiss the old verities. Modern living in assembly lines and discotheques, at cocktail parties, and in front of television completes the effacement. They smother whatever remains. No matter. Physicians can find meaning in their lives—in their work. We can busy ourselves with medicine, roentgenograms, laboratory tests, and operations. Perhaps the rest of the world lacks purpose but not ours. After all, Hippocrates gave
Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow
Authors: Anna Mansour, Grazia Abou-Ezzi, Ewa Sitnicka, Sten Eirik W. Jacobsen, Abdelilah Wakkach, Claudine Blin-Wakkach
Journal: The Journal of Experimental Medicine (2012)

Formation of the hematopoietic stem cell (HSC) niche in bone marrow (BM) is tightly associated with endochondral ossification, but little is known about the mechanisms involved. We used the oc/oc mouse, a mouse model with impaired endochondral ossification caused by a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the HSC niche formation. The absence of OCL activity resulted in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the BM. Restoration of OCL activity reversed the defect in HSC niche formation. Our data demonstrate that OBLs are required for establishing HSC niches and that osteoblastic development is induced by OCLs. These findings broaden our knowledge of the HSC niche formation, which is critical for understanding normal and pathological hematopoiesis.
Functionalized Nanoscale Micelles with Brain Targeting Ability and Intercellular Microenvironment Biosensitivity for Anti‐Intracranial Infection Applications
Authors: Kun Shao, Yu Zhang, Ning Ding, Shixian Huang, Jiqin Wu, Jianfeng Li, Chunfu Yang, Qibin Leng, Liya Ye, Jinning Lou, Liping Zhu, Chen Jiang
Journal: Advanced Healthcare Materials (2014)

Due to complication factors such as blood‐brain barrier (BBB), integrating high efficiency of brain target ability with specific cargo releasing into one nanocarrier seems more important. A brain targeting nanoscale system is developed using dehydroascorbic acid (DHA) as targeting moiety. DHA has high affinity with GLUT1 on BBB. More importantly, the GLUT1 transportation of DHA represents a “one‐way” accumulative priority from blood into brain. The artificial micelles are fabricated by a disulfide linkage, forming a bio‐responsive inner barrier, which can maintain micelles highly stable in circulation and shield the leakage of entrapped drug before reaching the targeting cells. The designed micelles can cross BBB and be further internalized by brain cells. Once within the cells, the drug release can be triggered by high intracellular level of glutathione (GSH). Itraconazole (ITZ) is selected as the model drug because of its poor brain permeability and low stability in blood. It demonstrates that the functionalized nanoscale micelles can achieve highly effective direct drug delivery to targeting site. Based on the markedly increased stability in blood circulation and improved brain delivery efficiency of ITZ, DHA‐modified micelles show highly effective in anti‐intracranial infection. Therefore, this smart nanodevice shows a promising application for the treatment of brain diseases.
707 LONG-TERM DE-NOVO LAMIVUDINE + ADEFOVIR COMBINATION THERAPY IN CHRONIC HEPATITIS B IS EFFICIENT, BUT HAS NEGATIVE IMPACT ON RENAL/BONE SAFETY IN COMPARISON TO ENTECAVIR MONOTHERAPY
Authors: I. Carey, A. Mendes, D. Joshi, M. Bruce, S. Knighton, A. Scalori, A. Gera, S. Hughes, M. Al-Freah, A. Suddle, K. Agarwal, P.M. Harrison
Journal: Journal of Hepatology (2011)
Increase in ascites white blood cell and protein concentrations during diuresis in patients with chronic liver disease
Authors: John C. Hoefs
Journal: Hepatology (1981)

Serum and ascites protein concentration and ascites cell concentration alterations with determined serially during diuresis in 27 patients with uncomplicated liver disease. The total protein concentration in ascites increased from 1.38 +/- 0.96 gm% to 2.86 +/- 1.28 gm% (p less than 0.001); the serum protein concentration from 6.26 +/- 0.81 gm% to 7.24 +/- 0.93 gm% (p less than 0.001), and the ascites to serum ratio of the total protein concentration from 0.21 +/- 0.13 to 0.38 +/- 0.14 (p less than 0.001). The white blood cell (WBC) concentration in ascites increased from 289 +/- 179 cells per mm3 to 1,108 +/- 924 cells per mm3 (p less than 0.001). Despite the increase in WBC concentration, the polymorphonuclear cell concentration remained constant (42 +/- 52 cells per mm3 to 68 +/- 96 cells per mm3). Protein concentration of the ascitic fluid greater than 3.0 gm% was demonstrated in 12 patients before completion of diuresis and ascitic fluid WBC concentration was greater than 750 cells per mm3 in 17 patients. Ten of 27 patients eventually developed ascites which had a combination of more than 3.0 gm% total protein concentration and greater than 750 cells per mm3. Ascitic fluid protein and WBC concentrations are not "fixed" at a low level in chronic liver disease since each rose during diuresis. Thus, the interpretation of these parameters must be made with caution in patients following significant diuresis.
Hemodynamic effects of elevated cerebrospinal fluid pressure: alterations with adrenergic blockade
Authors: Richard E. Brashear, Joseph C. Ross
Journal: Journal of Clinical Investigation (1970)

The cardiovascular effects of elevated cerebrospinal fluid (CSF) pressure were studied in 18 dogs, 6 in a control group, 6 after alpha adrenergic blockade, and 6 after beta adrenergic blockade. Vascular pressures did not change until CSF pressure was increased from 100 mm Hg to 200 mm Hg. In the control group, the aortic, pulmonary arterial, wedge, and right atrial pressures increased significantly. Cardiac output, heart rate, and stroke volume increased but systemic and pulmonary vascular resistances did not change. In the alpha adrenergic blockade group, vascular pressures did not increase after elevation of CSF pressure. Cardiac output increased or did not change, stroke volume increased, systemic resistance decreased, and pumonary resistance did not change. In the beta adrenergic blockade group, the vascular pressures all increased significantly when CSF pressure was elevated, but cardiac output did not change. Systemic resistance increased and pulmonary resistance decreased. Central blood volume increased in all three groups when CSF pressure was 200 mm Hg. The data suggest that a large and distinct alpha and beta adrenergic stimulus occurred when CSF pressure was increased to 200 mm Hg.
Hepatic iron overload in aceruloplasminaemia
Authors: N E Hellman
Journal: Gut (2000)

We report the case of a 52 year old male with diabetes mellitus and long standing evidence of hepatic iron excess. Initially considered to have haemochromatosis, this patient was reevaluated when hepatic iron stores were found to be unaffected by a prolonged course of weekly phlebotomy. The development of neurological disease prompted diagnostic consideration of aceruloplasminaemia, which we confirmed by demonstration of a novel frameshift mutation in the ceruloplasmin gene. Our inability to resolve the patient9s iron overload by regular phlebotomy is consistent with recent animal studies indicating an essential role for ceruloplasmin in cellular iron efflux. Evaluation of this case underscores the clinical relevance of aceruloplasminaemia in the differential diagnosis of hepatic iron overload and provides insight into the pathogenetic mechanisms of hepatocellular iron storage and efflux.
Ascitic fluid adenosine deaminase insensitivity in detecting tuberculous peritonitis in the United States
Authors: D J Hillebrand, B A Runyon, W G Yasmineh, G P Rynders
Journal: Hepatology (1996)

Tuberculous peritonitis, although common in Third World countries, remains an uncommon cause of ascites in the United States. Ascitic fluid adenosine deaminase (ADA) activity has been proposed as a useful diagnostic test. The aim of this retrospective study was to determine the clinical utility of ascitic fluid ADA activity in diagnosing tuberculous peritonitis in a U.S. patient population. A total of 368 ascitic fluid specimens from a well–characterized ascitic fluid bank, including tuberculous peritonitis (n = 7), tuberculous peritonitis in the setting of cirrhosis (n = 10), and consecutive specimens of widely varied etiologies (n = 351) were analyzed for ADA activity by ultraviolet spectrophotometry at 265 nm. The overall sensitivity of the ADA determination in diagnosing tuberculous peritonitis was only 58.8%, and the specificity was 95.4%. The accuracy of ADA determination (93.8%) compared favorably with that of the common ascitic fluid tests of white blood cell (WBC) count (&gt;500/mm3), total protein (&gt;2.5 g/dL), and combined WBC count and total protein (45.8%, 74.4%, and 81.3%, respectively). However, ADA was only 30% sensitive in detecting tuberculous peritonitis in the setting of cirrhosis, and cirrhosis was present in 59% of the tuberculous peritonitis patients in our population. In addition, malignancy–related ascites (13%) and bacterial peritonitis specimens (5.8%) occasionally yielded false–positive results. In conclusion, our results indicate that the ascitic fluid ADA activity has good accuracy but poor sensitivity and imperfect specificity in a U.S. patient population in which the prevalence of tuberculosis is low and underlying cirrhosis is common.
STUDIES ON GALL BLADDER FUNCTION
Authors: Cecilia Riegel, C. G. Johnston, I. S. Ravdin
Journal: The Journal of Experimental Medicine (1932)

The data obtained from the experiments on dogs reported in this paper lead us to conclude that bile pigment is not absorbed from the gall bladder bile. The mean loss of pigment is so small when compared with the amount of water lost that it is negligible. Our cholesterol data do not support the concept that this substance is secreted into the gall bladder bile of the dog under normal conditions. In the majority of experiments there was a loss of cholesterol. Indeed we have failed to find any evidence of definite secretion or absorption save in the case of the infected gall bladder. We are led to conclude, as did Rous and McMaster (15) with regard to bile pigment, that normally there is no absorption of cholesterol.
Randomized Phase II Trial of Sequential Chemotherapy in Advanced Non-Small Cell Lung Cancer (SWOG 9806)
Authors: Martin J. Edelman, Joseph I. Clark, Kari Chansky, Kathy Albain, Nirmala Bhoopalam, Geoffrey R. Weiss, Jeffrey K. Giguere, Karen Kelly, John Crowley, David R. Gandara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC. Experimental Design: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0–1 and normal organ function were eligible. Therapy: arm 1, carboplatin (area under the curve = 5.5 mg/ml × min day 1) and gemcitabine (1000 mg/m2 days 1 and 8 every 21 days × 3) followed by paclitaxel (225 mg/m2 every 21 days × 3) or arm 2, cisplatin (100 mg/m2 day 1), vinorelbine (25 mg/m2 days 1 and 8 every 21 d × 3) followed by docetaxel (75–100 mg/m2 every 21 days × 3). Results: Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively. Conclusions: Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.
Suicide after Leaving the UK Armed Forces —A Cohort Study
Authors: Navneet Kapur, David While, Nick Blatchley, Isabelle Bray, Kate Harrison
Journal: PLoS Medicine (2009)

Background Few studies have examined suicide risk in individuals once they have left the military. We aimed to investigate the rate, timing, and risk factors for suicide in all those who had left the UK Armed Forces (1996–2005). Methods and Findings We carried out a cohort study of ex-Armed Forces personnel by linking national databases of discharged personnel and suicide deaths (which included deaths receiving either a suicide or undetermined verdict). Comparisons were made with both general and serving populations. During the study period 233,803 individuals left the Armed Forces and 224 died by suicide. Although the overall rate of suicide was not greater than that in the general population, the risk of suicide in men aged 24 y and younger who had left the Armed Forces was approximately two to three times higher than the risk for the same age groups in the general and serving populations (age-specific rate ratios ranging from 170 to 290). The risk of suicide for men aged 30–49 y was lower than that in the general population. The risk was persistent but may have been at its highest in the first 2 y following discharge. The risk of suicide was greatest in males, those who had served in the Army, those with a short length of service, and those of lower rank. The rate of contact with specialist mental health was lowest in the age groups at greatest risk of suicide (14% for those aged under 20 y, 20% for those aged 20–24 y). Conclusions Young men who leave the UK Armed Forces were at increased risk of suicide. This may reflect preservice vulnerabilities rather than factors related to service experiences or discharge. Preventive strategies might include practical and psychological preparation for discharge and encouraging appropriate help-seeking behaviour once individuals have left the services.
Flavopiridol, Fludarabine, and Rituximab in Mantle Cell Lymphoma and Indolent B-Cell Lymphoproliferative Disorders
Authors: Thomas S. Lin, Kristie A. Blum, Diane Beth Fischer, Sarah M. Mitchell, Amy S. Ruppert, Pierluigi Porcu, Eric H. Kraut, Robert A. Baiocchi, Mollie E. Moran, Amy J. Johnson, Larry J. Schaaf, Michael R. Grever, John C. Byrd
Journal: Journal of Clinical Oncology (2009)

Purpose Flavopiridol downmodulates antiapoptotic proteins associated with resistance to fludarabine and rituximab and is effective against p53-mutated chronic lymphocytic leukemia (CLL). We conducted a phase I study of flavopiridol, fludarabine, and rituximab (FFR) in patients with mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's lymphomas (B-NHL), and CLL to determine the activity of FFR. Patients and Methods Therapy included fludarabine 25 mg/m 2 intravenously (IV) days 1 to 5 and rituximab 375 mg/m 2 day 1 every 28 days for 6 cycles. We administered flavopiridol 50 mg/m 2 by 1-hour IV bolus (IVB) day 1 (n = 15); day 1 to 2 (n = 6); 20 mg/m 2 30-minute IVB + 20 mg/m 2 4-hour IV infusion (n = 3); or 30 mg/m 2 + 30 mg/m 2 (n = 14). Results Thirty-eight patients (median age, 62 years) with MCL (n = 10); indolent B-NHL including follicular (n = 9), marginal zone (n = 4), lymphoplasmacytic (n = 1), or small lymphocytic lymphoma (n = 3); and CLL (n = 11), were enrolled. Twenty-two patients were previously untreated; 16 had received one to two prior therapies. Two patients in cohort 2 developed grade 3 dose-limiting toxicity (seizures, renal insufficiency). The median number of treatment cycles was 4, with cytopenias (n = 10) and fatigue (n = 3) the most common reasons for early discontinuation. Overall response rate was 82% (complete response, 50%; unconfirmed complete response, 5%; partial response, 26%), including 80% of patients with MCL (median age, 68; seven complete responses, one partial response). Median progression-free survival (PFS) was 25.6 months. Median PFS of patients with nonblastoid variant MCL (n = 8) was 35.9 months. Conclusion FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy.
Serum YKL-40 and Interleukin 6 Levels in Hodgkin Lymphoma
Authors: Robert J. Biggar, Julia S. Johansen, Karin Ekström Smedby, Klaus Rostgaard, Ellen T. Chang, Hans-Olov Adami, Bengt Glimelius, Daniel Molin, Stephen Hamilton-Dutoit, Mads Melbye, Henrik Hjalgrim
Journal: Clinical Cancer Research (2008)

Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis Hodgkin lymphoma.We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear regression, adjusting for age and sex.Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, P<0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients (n=176), levels were correlated with more advanced stages (P(trend), 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment onset had significantly lower levels than pretreatment patients; however, even >or=6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased compared with controls. In patients who died (n=12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly.Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.
822-2 Is sirolimus-eluting stent better than brachytherapy to treat in-stent restenosis at longer (12-month) follow-up? Angiographic and intravascular ultrasound analysis
Authors: Fausto Feres, Juan S Muñoz, Alexandre Abizaid, Rodolfo Staico, Luiz A Mattos, Galo Maldonado, Marinella Centemero, Ibraim Pinto, Andrea S Abizaid, Aurea Chaves, Luiz F Tanajura, Amanda Sousa, J Eduardo Sousa
Journal: Journal of the American College of Cardiology (2004)
Myocardial Cell and Sarcomere Lengths in the Normal Dog Heart
Authors: MICHAEL M. LAKS, MICHAEL J. NISENSON, H. J. C. SWAN
Journal: Circulation Research (1967)

The purpose of this study was to measure myocardial cell and sarcomere lengths at the bases and apices of the right (RV) and left ventricle (LV) of 4 normal canine hearts. The RV and LV were simultaneously fixed with glutaraldehyde at zero transmural pressure. Sections of trabeculae carneae were taken from the 1 cm cut at the bases (free wall) of the RV and LV. They were further fixed with osmium tetroxide, embedded in Epon 812, sectioned at ½ to 1 µ and stained with azure II and methylene blue. Measured from photomicrographs (X 1,000) taken with the phase microscope, mean cell length was 70.9 µ±1.49 (SEM); no statistical difference existed between the cell lengths at the bases and apices of the RV and LV. From adjacent tissue, the measurements of sarcomere lengths made from photomicrographs (phase microscope, oil immersion lens, enlarged to X 4,000) were not statistically different from those made with the electron microscope (P&gt;0.9). The sarcomere lengths at the LV base were the shortest-2.16 µ±0.002 (SEM), followed by the LV apex, 2.28 µ±0.005 (SEM); RV base, 2.41 µ±0.006 (SEM); and RV apex, 2.46 µ±0.003 (SEM). These variations in sarcomere length show the importance of specifying the site of sampling of myocardial tissue. The sarcomere lengths were related inversely to the thickness of the ventricular wall. This observation may be considered the structural reflection of the lesser distensibility of the left base as compared with the right apex, and may be simply the manifestation of the fact that the left base contains more muscle fibers.