tbuckley/cabot-search huggingface dataset:
Myelin from Human Peripheral Nerves QUANTITATIVE AND QUALITATIVE STUDIES IN TWO AGE GROUPS
Authors: Norton Spritz, Harbhajan Singh, Barbara Geyer
Journal: Journal of Clinical Investigation (1973)

Myelin in femoral nerve segments obtained at autopsy was isolated quantitatively by a series of discontinuous and continuous flotation procedures. The total amount of myelin isolated from these nerves was expressed as the sum of cholesterol, glycolipid, phospholipid, and protein and averaged 2.6±0.4 mg/g in a group aged 60-77 yr compared with 10.8±1.9 mg/g of nerve in a group aged 35-58 yr. The lower value in the older group remained apparent whether the myelin content was related to the whole nerve segment, its unit length or weight. This indicates that the decrease is an absolute one, not related to a change with aging in the nonmyelin content of nerve.
Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin’s Lymphoma Classification Project
Authors: T. Rüdiger, D.D. Weisenburger, J.R. Anderson, J.O. Armitage, J. Diebold, K.A. MacLennan, B.N. Nathwani, F. Ullrich, H.K. Müller-Hermelink
Journal: Annals of Oncology (2002)

BackgroundPeripheral T-cell lymphoma (PTCL) is rare in most parts of the world. Therefore, we have evaluated the 96 cases of PTCL diagnosed within the Non-Hodgkin’s Lymphoma Classification Project (NHLCP) (1378 cases) for their geographical distribution, pathologic features and diagnostic reliability, as well as clinical presentation and outcome.Materials and methodsDiagnoses of all cases were rendered independently by five experienced hematopathologists based on morphology only, and after introduction of the immunophenotype and clinical data. Divergent diagnoses were jointly discussed and a final consensus diagnosis was established in each case. Reliability of the diagnoses was evaluated statistically, and the clinical features and outcome were analyzed according to the consensus diagnoses.ResultsSeven per cent of all non-Hodgkin’s lymphoma (NHL) cases reviewed were classified as PTCL and the frequency varied from 1.5% to 18.3% in different countries. The interobserver agreement with the consensus diagnosis of PTCL was 86% in the Revised European–American Lymphoma (REAL) classification, but the designation of subtypes was less reliable. Diagnostic reliability improved from 41% to 86% after immunophenotyping, but did not improve further with the addition of detailed clinical data. Clinically, angiocentric nasal lymphoma presented in young females (median age 49 years) at extranodal sites, but with few adverse risk factors, whereas angioimmunoblastic lymphoma presented most often in older males (median age 65 years) at nodal and extranodal sites with numerous risk factors. The 5-year overall and failure-free survivals for patients with PTCL treated with doxorubicin (Adriamycin)-containing regimens were only 26% and 20%, respectively. Both failure-free and overall survival were strongly correlated with the performance status and International Prognostic Index scores at presentation, but differences in survival were not observed between the major histological types. However, within the PTCL ‘not otherwise specified’ category, but not angioimmunoblastic lymphoma, the number of transformed blasts was prognostically relevant.ConclusionsPTCLs can be diagnosed reliably by experienced hematopathologists, but immunophenotyping is absolutely necessary. Currently, all types of PTCL should be considered high-grade lymphomas. An increased ability to distinguish T-lymphocyte subsets is needed in order to better subclassify the PTCLs for therapeutic and prognostic purposes.
Safety and Efficacy of FOLFOX Followed by Cetuximab for Metastatic Colorectal Cancer With Severe Liver Dysfunction
Authors: Raymond Elsoueidi, Jessica Craig, Hesham Mourad, Elie M. Richa
Journal: Journal of the National Comprehensive Cancer Network (2014)

Both 5-FU and oxaliplatin have been used as single agents in patients with colorectal cancer and severe liver dysfunction, but the combination of these drugs has not yet been investigated. A 67-year-old man diagnosed with colorectal cancer in 2008 presented in April 2011 to Appalachian Regional Healthcare Cancer Center with obstructive jaundice and weight loss. Imaging studies were compatible with a liver mass and dilatation of the intrahepatic bile ducts. A liver biopsy confirmed metastatic colorectal cancer. Because his total bilirubin level was 23.1 mg/dL, a percutaneous catheter was placed in May 2011. His total bilirubin level decreased to 5.9 mg/dL, but then increased to 9.4 mg/dL in June 2011. He was started on a FOLFOX regimen, with a 50% dose reduction of 5-FU bolus (200 mg/m2) and continuous infusion (1200 mg/m2) over 46 hours, and a 15% dose reduction of oxaliplatin (75 mg/m2) every 2 weeks. He tolerated this regimen very well, with normalization of his bilirubin level, a significant decrease in his tumor markers, and a partial response seen on PET/CT scan. His only significant toxicity was a grade 2 stomatitis. He received 21 cycles of FOLFOX, and was later switched to cetuximab treatment after disease progression. These findings suggest that FOLFOX might be effective in metastatic colon cancer with severe liver dysfunction, with minimal toxicity, and deserves further investigation.
Vasopressin 1a receptor partial agonism increases sodium excretion and reduces portal hypertension and ascites in cirrhotic rats
Authors: Guillermo Fernández‐Varo, Denise Oró, Edward Earl Cable, Vedrana Reichenbach, Silvia Carvajal, Bernardino González de la Presa, Kazimierz Wiśniewski, Pere Ginés, Geoffrey Harris, Wladimiro Jiménez
Journal: Hepatology (2015)

Patients and rats with cirrhosis and ascites have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. We assessed the potential therapeutic value of a new V 1 a ‐AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE 204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE 204038, terlipressin, or vehicle were investigated. Mean arterial pressure and PP were continuously recorded and cardiac output and systemic vascular resistance (SVR) assessed at 30‐minute intervals for 90 minutes. Urine volume, urine osmolality, and urinary excretion of sodium and creatinine were measured in basal conditions and following twice‐daily subcutaneous doses of FE 204038 or vehicle. PP, mean arterial pressure, cardiac output, SVR, and ascites volume were also measured after 6 days. The expression of an array of vasoactive genes was assessed in the thoracic aorta and the mesenteric circulation of control rats and rats with cirrhosis and ascites. FE 204038 dose‐dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V 1a ‐AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE 204038. V 1a ‐AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. Conclusion: FE 204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V 1a ‐AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis. (H epatology 2016;63:207–216)
Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study
Authors: Antje Schuster, Cynthia Haliburn, Gerd Döring, Martin Harris Goldman
Journal: Thorax (2012)

<h3>Purpose</h3> To assess efficacy and safety of a new dry powder formulation of inhaled colistimethate sodium in patients with cystic fibrosis (CF) aged ≥6 years with chronic <i>Pseudomonas aeruginosa</i> lung infection. <h3>Study design and methods</h3> A prospective, centrally randomised, phase III, open-label study in patients with stable CF aged ≥6 years with chronic <i>P aeruginosa</i> lung infection. Patients were randomised to Colobreathe dry powder for inhalation (CDPI, one capsule containing colistimethate sodium 1 662 500 IU, twice daily) or three 28-day cycles with twice-daily 300 mg/5 ml tobramycin inhaler solution (TIS). Study duration was 24 weeks. <h3>Results</h3> 380 patients were randomised. After logarithmic transformation of data due to a non-normal distribution, adjusted mean difference between treatment groups (CDPI vs TIS) in change in forced expiratory volume in 1 s (FEV<sub>1</sub>% predicted) at week 24 was −0.98% (95% CI −2.74% to 0.86%) in the intention-to-treat population (n=373) and −0.56% (95% CI −2.71% to 1.70%) in the per protocol population (n=261). The proportion of colistin-resistant isolates in both groups was ≤1.1%. The number of adverse events was similar in both groups. Significantly more patients receiving CDPI rated their device as ‘very easy or easy to use’ (90.7% vs 53.9% respectively; p&lt;0.001). <h3>Conclusion</h3> CDPI demonstrated efficacy by virtue of non-inferiority to TIS in lung function after 24 weeks of treatment. There was no emergence of resistance of <i>P aeruginosa</i> to colistin. Overall, CDPI was well tolerated. <h3>Trial Reg No</h3> EudraCT 2004-003675-36.
FOLFIRINOX: A Great Leap Forward, but for Whom?
Authors: Lucas Vieira dos Santos, Diocésio Pinto de Andrade, João Paulo Lima
Journal: Journal of Clinical Oncology (2011)

by Ko 1 in the Comments and Controversies section.We do believe FOLFIRINOX (biweekly bolus plus infusional fluorouracil, leuco-vorin, irinotecan, and oxaliplatin) is a major step forward for patients with pancreatic cancer, and it must be considered the new backbone for clinical practice and also for therapy development. 2n his report, Ko 1 briefly discusses the influence of ethnical factors in toxicity.Several factors related to the patient as well as tumor biology can greatly interfere with the clinical outcomes of those with pancreatic cancer.A better understanding of these predictors of
Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Andrzej J. Jakubowiak, Don M. Benson, William Bensinger, David S.D. Siegel, Todd M. Zimmerman, Ann Mohrbacher, Paul G. Richardson, Daniel E.H. Afar, Anil K. Singhal, Kenneth C. Anderson
Journal: Journal of Clinical Oncology (2012)

To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m(2) IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria.Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months.The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.
Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck
Authors: Zhongqiu Wang, Erich M Sturgis, Fenghua Zhang, Dapeng Lei, Zhensheng Liu, L i Xu, Xicheng Song, Qingyi Wei, Guojun Li
Journal: Molecular Cancer (2012)

Abstract Background Cell cycle deregulation is common in human cancer, and alterations of p27 and p21 , two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN). Methods A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk. Results We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27 109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes ( P trend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6). Conclusions These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.
Iron-Binding Proteins and Risk of Cancer in Taiwan2
Authors: Richard G. Stevens, R. Palmer Beasley, Baruch S. Blumberg
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Iron-Binding Proteins and Risk of Cancer in Taiwan Get access Richard G. Stevens, Richard G. Stevens Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Palmer Beasley, R. Palmer Beasley Search for other works by this author on: Oxford Academic PubMed Google Scholar Baruch S. Blumberg Baruch S. Blumberg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 605–610, https://doi.org/10.1093/jnci/76.4.605 Published: 01 April 1986 Article history Received: 06 June 1985 Accepted: 21 November 1985 Published: 01 April 1986
Scaling Up Chronic Disease Prevention Interventions in Lower- and Middle-Income Countries
Authors: Thomas A. Gaziano, Neha Pagidipati
Journal: Annual Review of Public Health (2013)

Chronic diseases are increasingly becoming a health burden in lower- and middle-income countries, putting pressure on public health efforts to scale up interventions. This article reviews current efforts in interventions on a population and individual level. Population-level interventions include ongoing efforts to reduce smoking rates, reduce intake of salt and trans-fatty acids, and increase physical activity in increasingly sedentary populations. Individual-level interventions include control and treatment of risk factors for chronic diseases and secondary prevention. This review also discusses the barriers in interventions, particularly those specific to low- and middle-income countries. Continued discussion of proven cost-effective interventions for chronic diseases in the developing world will be useful for improving public health policy.
Crucial Roles for Protein Kinase C Isoforms in Tumor-Specific Killing by Apoptin
Authors: Jie Jiang, Daryl Cole, Nigel Westwood, Lee Macpherson, Farzin Farzaneh, Ghulam Mufti, Mahvash Tavassoli, Joop Gäken
Journal: Cancer Research (2010)

Abstract The chicken anemia virus–derived protein apoptin induces apoptosis in a variety of human malignant and transformed cells but not in normal cells. However, the mechanisms through which apoptin achieves its selective killing effects are not well understood. We developed a lentiviral vector encoding a green fluorescent protein–apoptin fusion gene (LV-GFP-AP) that can efficiently deliver apoptin into hematopoietic cells. Apoptin selectively killed the human multiple myeloma cell lines MM1.R and MM1.S, and the leukemia cell lines K562, HL60, U937, KG1, and NB4. In contrast, normal CD34+ cells were not killed and maintained their differentiation potential in multilineage colony formation assays. In addition, dexamethasone-resistant MM1.R cells were found to be more susceptible to apoptin-induced cell death than the parental matched MM1.S cells. Death susceptibility correlated with increased phosphorylation and activation of the apoptin protein in MM1.R cells. Expression array profiling identified differential kinase profiles between MM1.R and MM1.S cells. Among these kinases, protein kinase Cβ (PKCβ) was found by immunoprecipitation and in vitro kinase studies to be a candidate kinase responsible for apoptin phosphorylation. Indeed, shRNA knockdown or drug-mediated inhibition of PKCβ significantly reduced apoptin phosphorylation. Furthermore, apoptin-mediated cell death proceeded through the upregulation of PKCβ, activation of caspase-9/3, cleavage of the PKCδ catalytic domain, and downregulation of the MERTK and AKT kinases. Collectively, these results elucidate a novel pathway for apoptin activation involving PKCβ and PKCδ. Further, they highlight the potential of apoptin and its cellular regulators to purge bone marrow used in autologous transplantation for multiple myeloma. Cancer Res; 70(18); 7242–52. ©2010 AACR.
Improved Survival of Follicular Lymphoma Patients in the United States
Authors: Wade T. Swenson, James E. Wooldridge, Charles F. Lynch, Valerie L. Forman-Hoffman, Elizabeth Chrischilles, Brian K. Link
Journal: Journal of Clinical Oncology (2005)

Despite several new treatment options, single- and multi-institution analyses have not clarified whether survival patterns in follicular lymphoma (FL) patients have changed in recent decades. We undertook a study using a large population-based registry to analyze survival patterns among patients with FL.Surveillance, Epidemiology, and End Results morphology codes were used to identify 14,564 patients diagnosed with FL between 1978 and 1999. Observed median survival times, Kaplan-Meier survival curves, proportional death hazard ratios, and relative survival rates were calculated. Joinpoint regression analysis was used to identify trends in annual adjusted death hazard ratios.An improvement in survival of all patients with FL was observed between each of three diagnosis eras (1978 to 1985, 1986 to 1992, and 1993 to 1999) by log-rank tests. Among patients with stage-specific data, the median survival time improved from 84 months (95% CI, 81 to 88 months) in the 1983 to 1989 era to 93 months (95% CI, 89 to 97 months) in the 1993 to 1999 era. Similar findings were identified across sex and age groups and for subsets including advanced-stage, large-cell FL and the combined subset of small cleaved- and mixed-cell FL. The inter-era survival advantage observed in white patients was not observed for black patients. The relative risk of death decreased by 1.8% per year over the 1983 to 1999 observation period.The survival of patients with FL in the United States has improved over the last 25 years. The survival improvement may be a result of the sequential application of effective therapies and improved supportive care.
Exercise-induced flow limitation, dynamic hyperinflation and exercise capacity in patients with bronchial asthma
Authors: E.N. Kosmas, J. Milic-Emili, A. Polychronaki, I. Dimitroulis, S. Retsou, M. Gaga, A. Koutsoukou, Ch. Roussos, N.G. Koulouris
Journal: European Respiratory Journal (2004)

It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WR max ). A total of 20 asthmatics in a stable condition and aged 32±13 yrs (mean± sd ) with a forced expiratory volume in one second (FEV 1 ) of 101±21% of the predicted value were studied. Only three patients exhibited an FEV 1 below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W·min −1 ) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH ( via reduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WR max . FEV 1 was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WR max . Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WR max 75±9% pred) compared to the seven non-EFL patients (WR max 95±13% pred). Moreover, a significant correlation of WR max (% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WR max was found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients. In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.
Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene- and Aldrin-Metabolizing Activities in Cultured Human and Rat Hepatoma Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Limbosch
Journal: JNCI Journal of the National Cancer Institute (1983)

Five established hepatoma cell lines, 1 of rat origin and 4 derived from human liver carcinoma, were compared for their capacity to perform metabolic activation of one polycyclic hydrocarbon, benzo[a]pyrene (BP), and one cyclodiene chlorinated insecticide, aldrin. The results of these investigations indicated both species and individual differences among these cell lines. Aldrin was found to be converted into dieldrin much more efficiently by the rat hepatoma cell line than by any human cell lines, whereas 2 human lines displayed the highest BP-metabolizing activity whether measured as the amounts of water-soluble products or estimated by cytotoxic cell-mediated assays. Results also showed that one particular human cell line can replace, advantageously, V79 hamster cells as target in a cell-mediated assay owing to its incapability to metabolize BP and its high sensitivity to BP metabolites.