tbuckley/cabot-search huggingface dataset:
Absence of Class II–Associated Invariant Chain Peptide on Leukemic Blasts of Patients Promotes Activation of Autologous Leukemia-Reactive CD4+ T Cells
Authors: Marvin M. van Luijn, Willemijn van den Ancker, Martine E.D. Chamuleau, Adri Zevenbergen, Theresia M. Westers, Gert J. Ossenkoppele, S. Marieke van Ham, Arjan A. van de Loosdrecht
Journal: Cancer Research (2011)

Immune escape in cancer poses a substantial obstacle to successful cancer immunotherapy. Multiple defects in HLA class I antigen presentation exist in cancer that may contribute to immune escape, but less is known about roles for HLA class II antigen presentation. On class II(+) leukemic blasts, the presence of class II-associated invariant chain peptide (CLIP) is known to be correlated with poor survival in acute myeloid leukemia (AML). In this study, we evaluated the functional significance of CLIP expression on leukemic blasts of AML patients. CD4(+) T cells from patients were cocultured with autologous CLIP(-) and CLIP(+) primary leukemic blasts and analyzed for several functional parameters by flow cytometry. Increased HLA-DR and IFN-γ expression was observed for CD4(+) T cells stimulated with CLIP(-) leukemic blasts, in contrast to CLIP(+) leukemic blasts, which indicated an activation and polarization of the CD4(+) T cells toward T-helper 1 cells. In addition, CLIP(-) leukemic blasts induced greater outgrowth of effector memory CD4(+) T cells (with HLA-DR-restricted T-cell receptor Vβ repertoires) that were associated with better leukemia-specific reactivity than with CLIP(+) leukemic blasts. Our findings offer a clinical rationale to downmodulate CLIP on leukemic blasts as a strategy to degrade immune escape and improve leukemia-specific T-cell immunity in AML patients.
Diabetes and the World Health Organiiation: Progress towards prevention and control
Authors: Hilary King
Journal: Diabetes Care (1993)

Diabetes has a long history at WHO, and official relations were established between WHO and IDF as early as 1957. The WHO Expert Committee meeting on diabetes in 1979, and the first WHO Study Group on diabetes in 1985, each produced blue-book reports (1,2), which have become classics of the diabetes literature and for which demand continues to grow.
Pioglitazone and Rosiglitazone Have Different Effects on Serum Lipoprotein Particle Concentrations and Sizes in Patients With Type 2 Diabetes and Dyslipidemia
Authors: Mark A. Deeg, John B. Buse, Ronald B. Goldberg, David M. Kendall, Anthony J. Zagar, Scott J. Jacober, Mehmood A. Khan, Alfonzo T. Perez, Meng H. Tan
Journal: Diabetes Care (2007)

Associated with insulin resistance in type 2 diabetes are increased serum triglycerides, decreased HDL cholesterol, and a predominance of large VLDL, small LDL, and small HDL particles. The comparative effects of thiazolidinedione insulin sensitizers on serum lipoprotein particle concentrations and sizes in type 2 diabetes are not known. We studied the effects of pioglitazone (PIO) and rosiglitazone (ROSI) treatments on serum lipoprotein particle concentrations and sizes in type 2 diabetic patients with dyslipidemia.This is a prospective, randomized, double-blind, multicenter, parallel-group study. After a 4-week placebo washout period, patients randomized to PIO (n = 369) were treated with 30 mg q.d. for 12 weeks followed by 45 mg q.d. for another 12 weeks, while patients randomized to ROSI (n = 366) were treated with 4 mg q.d. followed by 4 mg b.i.d. for the same intervals. Lipoprotein subclass particle concentrations and sizes were determined by proton nuclear magnetic resonance spectroscopy at baseline and end point (PIO [n = 333] and ROSI [n = 325] patients).PIO treatment increased total VLDL particle concentration less than ROSI treatment and decreased VLDL particle size more than ROSI. PIO treatment reduced total LDL particle concentration, whereas ROSI treatment increased it. Both treatments increased LDL particle size, with PIO treatment having a greater effect. Whereas PIO treatment increased total HDL particle concentration and size, ROSI treatment decreased them; both increased HDL cholesterol levels.PIO and ROSI treatments have different effects on serum lipoprotein subclass particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.
Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials
Authors: Hiddo J Lambers Heerspink, Toshiharu Ninomiya, Sophia Zoungas, Dick de Zeeuw, Diederick E Grobbee, Meg J Jardine, Martin Gallagher, Matthew A Roberts, Alan Cass, Bruce Neal, Vlado Perkovic
Journal: The Lancet (2009)
Post traumatic osteoma of tibial insertion of medial collateral ligament of knee joint
Authors: V S Shanker, S Gadikoppula, M D Loeffler
Journal: British Journal of Sports Medicine (1998)

Two cases are presented of post traumatic para-articular osteoma developing at the site of tibial attachment of the medial collateral ligament of knee joint. These occurred after injuries sustained while playing football and in one case the ossified mass was treated with surgical excision for unresolved symptoms after conservative measures. A comparison is made with Pellegrini Stieda disease, which is a similar affection of the femoral insertion of the medial ligament of the knee joint.
Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis.
Authors: B W Robinson, T L McLemore, R G Crystal
Journal: Journal of Clinical Investigation (1985)

Gamma interferon (IFN gamma) is a potent immune mediator that plays a central role in enhancing cellular immune processes. This study demonstrates that while lung mononuclear cells from normal individuals spontaneously release little or no interferon (less than 10 U/10(6) cells per 24 h), those from patients with pulmonary sarcoidosis spontaneously release considerable amounts (65 +/- 20 U/10(6) cells per 24 h, P less than 0.02 compared to normals). Furthermore, cells from patients with active disease release far more interferon than those from patients with inactive disease (101 +/- 36 compared to 24 +/- 8 U/10(6) cells per 24 h, P less than 0.02). Characterization of this interferon using acid sensitivity, specific antibody inhibition, and target cell specificity criteria demonstrated that it was almost entirely IFN gamma. This spontaneous release of IFN gamma appeared to be compartmentalized to the lung of these patients in that their blood mononuclear cells spontaneously released little or no IFN gamma (P less than 0.02, compared to sarcoidosis lung mononuclear cells) and no IFN gamma was detected in their serum. Both lung T lymphocytes and alveolar macrophages contributed to the spontaneous release of IFN gamma by lung mononuclear cells from sarcoid patients; purified preparations of T lymphocytes and alveolar macrophages from these patients spontaneously released similar amounts of IFN gamma (56 +/- 21 and 32 +/- 11 U/10(6) cells per 24 h, respectively, P greater than 0.3). At least one role for IFN gamma in the pathogenesis of sarcoidosis appeared to be related to activation of alveolar macrophages, as alveolar macrophages recovered from patients with active disease spontaneously killed [3H]uridine-labeled tumor cell targets (17.7 +/- 4.5% cytotoxicity compared with 2.8 +/- 0.9% in normals, P less than 0.02) and purified IFN gamma enhanced the ability of alveolar macrophages from sarcoidosis patients with inactive disease to kill similar targets (P less than 0.001, compared to alveolar macrophages cultured in medium alone). Treatment of sarcoid patients with corticosteroids, a therapy known to suppress the activity of the disease, caused a marked reduction in the level of spontaneous IFN gamma release by lung mononuclear cells compared with untreated patients (P less than 0.02), which suggests that the effectiveness of corticosteroid therapy in controlling active pulmonary sarcoidosis may, at least in part, be due to suppression of IFN gamma release.
Comparative Outcomes of Donor Graft CD34<sup>+</sup> Selection and Immune Suppressive Therapy As Graft-Versus-Host Disease Prophylaxis for Patients With Acute Myeloid Leukemia in Complete Remission Undergoing HLA-Matched Sibling Allogeneic Hematopoietic Cell Transplantation
Authors: Marcelo C. Pasquini, Steven Devine, Adam Mendizabal, Lindsey R. Baden, John R. Wingard, Hillard M. Lazarus, Frederick R. Appelbaum, Carolyn A. Keever-Taylor, Mary M. Horowitz, Shelly Carter, Richard J. O'Reilly, Robert J. Soiffer
Journal: Journal of Clinical Oncology (2012)

T-cell depletion (TCD) reduces the incidence of graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). However, concerns about relapse, graft rejection, and variability in technique have limited the widespread application of this approach.Outcomes of 44 patients receiving HLA-identical sibling TCD grafts using a uniform technique for CD34(+) selection as the sole form of immune suppression were compared with outcomes of 84 patients receiving T-replete grafts and pharmacologic immune suppression therapy (IST).Groups were similar, except for fewer men (36% with TCD v 56% with IST) and more frequent use of radiation-containing regimens (100% with TCD v 50% with IST) in the CD34-selected TCD cohort. The proportion of patients with neutrophil engraftment at day 28 was similar (96% with IST and 100% with TCD grafts). The 100-day rates of grade 2 to 4 acute GVHD were 39% and 23% with IST and TCD grafts, respectively (P = .07). Corresponding 2-year rates of chronic GVHD were lower with TCD grafts than IST (19% v 50%, respectively; P < .001). There were no differences in rates of graft rejection, leukemia relapse, treatment-related mortality, and disease-free and overall survival rates. At 1 year, 54% and 12% of patients were still on immunosuppression in the IST and TCD cohorts, respectively. TCD was associated with a higher GVHD-free survival at 2 years compared with IST (41% v 19%, respectively; P = .006).These results suggest that TCD via CD34 selection might lower long-term morbidity as a result of chronic GVHD without negatively impacting relapse rates in patients with acute myeloid leukemia. Additional prospective studies should be undertaken to definitively address the role of TCD in HCT.
New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia
Authors: Gérard Socié, Rochelle E. Curtis, H. Joachim Deeg, Kathleen A. Sobocinski, Alexandra H. Filipovich, Lois B. Travis, Keith M. Sullivan, Philip A. Rowlings, Douglas W. Kingma, Peter M. Banks, William D. Travis, Robert P. Witherspoon, Jean Sanders, Elaine S. Jaffe, Mary M. Horowitz
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P &lt; .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell–depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.
ADJUVANTS IN IMMUNIZATION WITH INFLUENZA VIRUS VACCINES
Authors: William F. Friedewald
Journal: The Journal of Experimental Medicine (1944)

Subcutaneous inoculation, of PR8 allantoic fluid, or watery suspensions of the virus obtained from allantoic fluid by high-speed centrifugation or by elution after adsorption on red cells induced serum antibodies in experimental animals, which reached the highest levels within 2 weeks after inoculation and were gradually lost thereafter. The addition of killed acid-fast bacteria (Myco. tuberculosis or butyricum), paraffin oil, and a proprietary adsorption base (Falba) to form a stable water-in-oil emulsion of influenza virus suspensions greatly enhanced and maintained immunity and antibody response to the virus. These adjuvants provided a much more effective method of increasing antibody production to the virus than the use of concentrated preparations of virus alone. Paraffin oil and Falba without the acid-fast bacilli were less effective as adjuvants, although the antibody levels induced were higher than those produced by watery suspensions of the virus and were maintained at a constant level for at least 6 months. Myco. butyricum appeared to be more effective in producing antibodies against the virus than the tubercle bacilli in the emulsions of paraffin oil and Falba. Immunization with these adjuvants and suspensions of influenza virus obtained from allantoic fluid induced antibodies not only against the virus but against antigenic material contained in normal allantoic fluid, although the latter titers were considerably lower. A suspension of influenza virus (sedimented by high-speed centrifugation) and Myco. butyricum in sesame oil induced about four times as much antibody as when the virus was suspended in saline, in sesame oil alone, or in combination with typhoid bacilli.
608 H2O2 RAPIDLY ACTIVATES THE SYSTEMIC IRON HORMONE HEPCIDIN INDEPENDENT OF THE IL-6/BMP6 NETWORK
Authors: G. Millonig, I. Ganzleben, G. Casanovas, T. Peccerella, M. Muckenthaler, H.K. Seitz, S. Mueller
Journal: Journal of Hepatology (2011)
Polymorphisms in the Genes Encoding for Human Kinin Receptors and the Risk of End-Stage Renal Failure
Authors: MARCIN J. ZYCHMA, JANUSZ GUMPRECHT, EWA ZUKOWSKA-SZCZECHOWSKA, WLADYSLAW GRZESZCZAK
Journal: Journal of the American Society of Nephrology (1999)

Abstract. There is evidence that environmental factors and genetic predisposition affect the development of end-stage renal disease (ESRD). The role of kinin peptides in renal pathology has been also suggested, and a nephroprotective effect of kinins, mediated by B1 and B2 kinin receptors, has been postulated. Recently, two novel sequence differences in the B1R gene were identified, and the C allele of the G→C substitution at position -699 in the promoter region of the B1R gene was found to be less frequent among patients with ESRD compared with healthy control subjects. In this study, the association between B1R and B2R polymorphisms and ESRD was examined using a family-based study design: transmission/disequilibrium test. B1R gene G→C substitution at position -699 in the promoter region and B2R gene C→T transition at position 181 in exon 2 were genotyped in 247 family trios: offspring affected with ESRD and both parents. The less common alleles of both polymorphisms (B1R C allele and B2R T allele) were transmitted from heterozygous parents to offspring affected with ESRD less frequently than expected (37 and 36%, respectively; P < 0.05). In conclusion, results obtained in this study support a hypothesis of the protective role of bradykinin receptor gene polymorphisms in the development of ESRD.
Schizophrenia as a model of context-deficient cortical computation
Authors: Steven M. Silverstein, Lindsay S. Schenkel
Journal: Behavioral and Brain Sciences (1997)

Phillips &amp; Singer's compelling presentation is weakest in its demonstration of commonalities between sensory plasticity and higher forms of learning and behavior. We propose that available data on schizophrenia can provide such evidence, because of the presence of impairments in a number of functions central to their model, and strong relationships between these dysfunctions and behavior.
MicroRNA-mediated regulation of melanoma
Authors: V. Sun, W.B. Zhou, S. Majid, M. Kashani-Sabet, A.A. Dar
Journal: British Journal of Dermatology (2014)

Melanoma is one of the most aggressive and deadly skin cancers, and, in its advanced stages, accounts for > 80% mortality. The incidence of melanoma is increasing worldwide; however, beyond surgical removal of the tumour, there is currently no curative therapy available, especially for its advanced stages. This may, in part, be owing to incomplete understanding of the molecular mechanisms that regulate the initiation and/or progression of melanoma to metastasis. The molecular mechanisms leading to the development and progression of melanoma are the focus of intense investigation, and many genetic/epigenetic alterations affecting melanoma progression and development have been identified. microRNAs (miRNAs) are emerging as important causal modulators in the development and progression of melanoma. The understanding of miRNA-mediated regulation of tumours has grown immensely over the last few years, as it has been understood to regulate most biological processes. Here, we review the currently available data on miRNAs associated with melanoma, highlighting those deregulated miRNAs that target important genes and pathways involved in the progression of melanocytes to primary and metastatic melanoma. We also review their potential clinical utility as biomarkers and potential use in targeted therapy.
Gastric Acid Secretion Rate and Buffer Content of the Stomach after Eating. RESULTS IN NORMAL SUBJECTS AND IN PATIENTS WITH DUODENAL ULCER
Authors: John S. Fordtran, John H. Walsh
Journal: Journal of Clinical Investigation (1973)

New methods are described by which the buffer content and the rate and pattern of net gastric acid secretion in human subjects fed normal meals can be measured by use of sodium bicarbonate infusion to control intragastric pH. With these techniques, it was shown that the rate of acid secretion in response to a steak meal in seven duodenal ulcer patients was twice the rate achieved in six control subjects and that the amount of acid secreted after eating exceeded the peak histamine response in the ulcer patients but not in the controls. Meal-stimulated acid secretion, expressed as a function of the peak histamine response, was roughly correlated with the serum gastrin concentration (r = 0.45), but it was concluded that other factors must also contribute to the higher than normal secretory responses to a meal found in duodenal ulcer patients. Measurement of buffer content of the stomach revealed that the duodenal ulcer patients emptied the meal buffer at a much more rapid rate than the normal subjects. By 2 h after eating, the ulcer subjects had less than half as much buffer in their stomachs as the controls. The combination of acid hypersecretion and rapid buffer emptying leads to abnormally high gastric acidity after a meal in duodenal ulcer patients. These results suggest that, in addition to a large parietal cell mass, parietal cell responsiveness to a meal and the rate of buffer emptying may be important in the pathogenesis of duodenal ulcer.
Preclinical Characterization of the Antiglioma Activity of a Tropism-Enhanced Adenovirus Targeted to the Retinoblastoma Pathway
Authors: J. Fueyo, R. Alemany, C. Gomez-Manzano, G. N. Fuller, A. Khan, C. A. Conrad, T.-J. Liu, H. Jiang, M. G. Lemoine, K. Suzuki, R. Sawaya, D. T. Curiel, W. K. A. Yung, F. F. Lang
Journal: JNCI Journal of the National Cancer Institute (2003)

Oncolytic adenoviruses are promising therapies for the treatment of gliomas. However, untargeted viral replication and the paucity of coxsackie-adenovirus receptors (CARs) on tumor cells are major stumbling blocks for adenovirus-based treatment. We studied the antiglioma activity of the tumor-selective Delta-24 adenovirus, which encompasses an early 1 A adenoviral (E1A) deletion in the retinoblastoma (Rb) protein-binding region, and of the Delta-24-RGD adenovirus. Delta-24-RGD has an RGD-4C peptide motif inserted into the adenoviral fiber, which allows the adenovirus to anchor directly to integrins.CAR and integrin expression were examined by flow cytometry in six glioma cell lines and in normal human astrocytes (NHAs). Adenoviral vectors containing green fluorescent protein (GFP) (AdGFP and AdGFP-RGD) were used to infect glioma cell lines with high or low CAR expression. Viability of glioma cells infected with different adenoviruses was assessed by trypan blue staining. Adenovirus replication was quantified with the infection-dose replication assay. Athymic mice carrying glioma xenografts received intratumoral injections of Delta-24-RGD or Delta-24 and were followed for survival, which was analyzed by the Kaplan-Meier method and the log-rank test. All statistical tests were two-sided.Half the glioma cell lines expressed low levels of CAR (defined as <50% of cells expressing detectable CAR); all lines expressed integrins in more than 50% of cells. Infection of U-87 MG cells (a low-CAR-expressing line) with AdGFP-RGD resulted in approximately six times more GFP-positive cells than infection with AdGFP. Delta-24-RGD was more cytopathic to both low- and high-CAR-expressing glioma lines than Delta-24, and it replicated more efficiently in both cell lines. In the xenografted mice, intratumoral injection of Delta-24-RGD was associated with longer survival than intratumoral injection of Delta-24 (P<.001, log-rank test). Furthermore, 60% of Delta-24-RGD-treated mice but only 15% of Delta-24-treated mice survived more than 4 months (difference = 45%, 95% CI = 21% to 68%).The antitumor activity of Delta-24-RGD suggests that it has the potential to be an effective agent in the treatment of gliomas.
Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER): a cost-effectiveness analysis
Authors: Sylvie Boyer, Laura March, Charles Kouanfack, Gabrièle Laborde-Balen, Patricia Marino, Avelin Fobang Aghokeng, Eitel Mpoudi-Ngole, Sinata Koulla-Shiro, Eric Delaporte, Maria Patrizia Carrieri, Bruno Spire, Christian Laurent, Jean-Paul Moatti
Journal: The Lancet Infectious Diseases (2013)