tbuckley/cabot-search huggingface dataset:
Receptor Selection in B and T Lymphocytes
Authors: David Nemazee
Journal: Annual Review of Immunology (2000)

The process of clonal selection is a central feature of the immune system, but immune specificity is also regulated by receptor selection, in which the fate of a lymphocyte’s antigen receptor is uncoupled from that of the cell itself. Whereas clonal selection controls cell death or survival in response to antigen receptor signaling, receptor selection regulates the process of V(D)J recombination, which can alter or fix antigen receptor specificity. Receptor selection is carried out in both T and B cells and can occur at different stages of lymphocyte differentiation, in which it plays a key role in allelic exclusion, positive selection, receptor editing, and the diversification of the antigen receptor repertoire. Thus, the immune system takes advantage of its control of V(D)J recombination to modify antigen receptors in such a way that self/non-self discrimination is enhanced. New information about receptor editing in T cells and B-1 B cells is also discussed.
Three cases of idiopathic bronchiolitis obliterans with organizing pneumonia
Authors: J Alegre-Martin, T Fernandez de Sevilla, F Garcia, V Falco, JM Martinez-Vazquez
Journal: European Respiratory Journal (1991)

Three patients with bronchiolitis obliterans organizing pneumonia are described. Chest X-ray films showed peripheral densities and pulmonary function tests a restrictive pattern. In all three cases transbronchial biopsy was not useful for diagnosis and we point out the importance of an open lung biopsy in order to make the differential diagnosis with other infiltrative lung disease with a different prognosis and therapy.
Effect of the 5-lipoxygenase inhibitor ZD2138 on allergen-induced early and late asthmatic responses.
Authors: S M Nasser, G S Bell, R J Hawksworth, K E Spruce, R MacMillan, A J Williams, T H Lee, J P Arm
Journal: Thorax (1994)

BACKGROUND--Leukotrienes are lipid mediators generated from arachidonic acid by the 5-lipoxygenase pathway which may play an important part in the pathophysiology of asthma. Previous studies have demonstrated attenuation of the allergen-induced early and late asthmatic responses by leukotriene receptor antagonists. The effect of the 5-lipoxygenase inhibitor ZD2138, a non-redox lipoxygenase inhibitor which inhibits leukotriene synthesis for 24 hours after single doses of 350 mg, on allergen-induced early and late asthmatic responses has been assessed. METHODS--Eight asthmatic subjects with baseline FEV1 &gt; 70% were studied. On screening, all subjects developed an allergen-induced biphasic asthmatic response to grass pollen, cat dander, or house dust mite. ZD2138 (350 mg) or placebo was given on two occasions separated by two weeks in a randomised double blind fashion. Allergen inhalation challenge was performed four hours after dosing and FEV1 was measured for eight hours. The inhibitory activity of ZD2138 on the 5-lipoxygenase pathway was assessed by measurements of calcium ionophore-stimulated generation of LTB4 in whole blood ex vivo and by analysis of urinary LTE4 levels before administration of drug or placebo and at regular intervals after oral drug dosing and allergen challenge. RESULTS--ZD2138 produced no significant bronchodilatation or attenuation of the early or late asthmatic response, although there was 82% inhibition of whole blood generation of LTB4 in response to calcium ionophore stimulation and 52% reduction in urinary excretion of LTE4. CONCLUSIONS--In asthmatic subjects the 5-lipoxygenase inhibitor ZD2138 did not protect against allergen-induced asthmatic responses, despite substantial inhibition of 5-lipoxygenase.
Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission
Authors: Jessica Wilks, Egil Lien, Amy N. Jacobson, Michael A. Fischbach, Nilofer Qureshi, Alexander V. Chervonsky, Tatyana V. Golovkina
Journal: Cell Host & Microbe (2015)
Gall stone disease in African patients with sickle cell anaemia: a preliminary report from Yaounde, Cameroon.
Authors: R F Billa, M S Biwole, A G Juimo, B I Bejanga, K Blackett
Journal: Gut (1991)

Cholecystosonography was undertaken in 90 patients with sickle cell disease aged 15 years and over. Gall stones were found in 26 (28.9%) patients. There was no sex difference, but the incidence increased with age from 13.2% at under 20 years to 75% at 30 years and over. The mean serum cholesterol and total and unconjugated bilirubin concentrations were not significantly different between patients with and without gall stones. As most (80.8%) stones were radiolucent they were probably of pigment type, containing little or no calcium, and further investigation into how they are produced is needed. Sickle cell patients with acute abdominal crisis should have gall bladder disease excluded before a diagnosis of vascular crisis is made.
Assessment of Long-Term Outcomes of Community-Acquired Hepatitis C Infection in a Cohort With Sera Stored From 1971 to 1975
Authors: Alison J. Rodger, Stuart Roberts, Anna Lanigan, Scott Bowden, Tracy Brown, Nick Crofts
Journal: Hepatology (2000)

The aim of this study was to examine the long-term effects of hepatitis C virus (HCV) infection on a cohort of patients admitted with acute viral hepatitis from 1971 through 1975. The availability of stored sera from this time enabled testing to identify those who were anti-HCV-positive on admission. Sixteen percent (n = 238) of the cohort tested anti-HCV-positive. The unexposed group was selected from those who were anti-HCV-negative. Systematic approaches were used to locate the cohort and health outcomes assessed by a study-specific questionnaire and clinical, serological, virological, and biochemical assessment. Complete follow-up was achieved on 98 anti-HCV-positive individuals and 201 negatives. Injecting drug use (IDU) was the presumed route of infection. At a mean of 25 years’ follow-up, 54% of the anti-HCV-positive group had evidence of chronic HCV infection (both anti-HCV- and HCV-RNA-positive); the remainder were HCV-RNA-negative. Sixty-nine percent of those chronically infected had elevated serum alanine transaminase (ALT) levels, but only 8% had progressed to overt cirrhosis, and no cases of hepatocellular carcinoma (HCC) were identified. In summary, anti-HCV-positive subjects were 8 times more likely to have died from suicide or drug overdose than from HCV-related disease. Anti-HCV-positive study subjects were at increased risk of liver-related pathology after 25 years’ follow-up, but few had progressed to overt cirrhotic liver disease. Excess mortality in this group was not the result of liver disease. This suggests that the natural history of community-acquired HCV may be more benign than previously thought.
The preparation and the in-vitro pharmacodynamics study of the intracapsular sustained-release preparations for the prevention of posterior capsule opacification
Authors: Qian Dong, Shaoling Yi, Zihang Peng, Chunshun Zhao
Journal: Asian Journal of Pharmaceutical Sciences (2013)

Docetaxel-loaded sustained-release preparation based on 2-Hydroxyethyl methacrylate (HEMA) and Methyl methacrylate (MMA) cross-linked copolymer (P(HEMA-co-MMA)) was prepared to examine the potential use for preventing posterior capsule opacification (PCO). The preparations were prepared by polymerizing the mixture of HEMA, MMA, cross-linking agent (EGDMA), initiator (AIBN) and docetaxel. The influence factors and mechanism of drug release were studied in the experiments. FT-IR, X-RD and SEM methods were used to characterize the polymer (P(HEMA-co-MMA)) and docetaxel-loaded sustained-release preparations. Biocompatibility of P(HEMA-co-MMA) and in-vitro effect of docetaxel-loaded sustained-release preparations were also evaluated. The results showed that docetaxel could release sustainedly from these preparations prepared by cross-linking polymerization. And the release rate could be accelerated by increasing the MMA ratio or EGDMA ratio of the polymer. Release mechanism of docetaxel fitted the Higuchi model well. The results of IR and X-RD showed that only a hydrogen bond was formed between docetaxel and P(HEMA-co-MMA). Docetaxel dispersed in P(HEMA-co-MMA) in amorphous form. The elution test showed that P(HEMA-co-MMA) had good biocompatibility and the in-vitro pharmacodynamics study proved that docetaxel could release stably from the preparations and inhibit HLECs' proliferation. The docetaxel-loaded sustained-release preparations proved to be a promising therapy for preventing PCO. These results also lay a theoretical and experimental foundation for the future.
Hepatitis B surface antigen levels at 6 months after treatment can predict the efficacy of lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B
Authors: Jeong Han Kim, Hee Won Moon, Soon Young Ko, Won Hyeok Choe, So Young Kwon
Journal: Clinical and Molecular Hepatology (2014)

Quantitation of hepatitis B surface antigen (HBsAg) is an increasingly popular method to determine the treatment response in chronic hepatitis B (CHB) patients. The clinical value of HBsAg level measurement during rescue therapy for lamivudine (LMV)-resistant CHB patients have not been evaluated to date. Therefore, this study investigated the correlation between HBsAg level and treatment response in LMV-resistant CHB patients treated with adefovir (ADV) add-on therapy.LMV-resistant CHB patients treated with LMV-ADV combination therapy for over 2 years were included. HBsAg levels were measured at 6 month intervals until 1 year, and annually thereafter. Treatment response was assessed by determining the virological response (VR, undetectable HBV DNA levels) during treatment.Fifty patients were included, of which 40 showed a VR. HBsAg levels were not different significantly at baseline (4.0 vs. 3.6 Log10 IU/mL, P=0.072). However, the HBsAg level decreased after 6 months of treatment in patients with a VR and became different significantly between the groups thereafter (3.9 vs. 3.3 at 6 months, P=0.002; 3.8 vs. 3.2 at 1 year, P=0.004; 3.9 vs. 3.2 at 2 years, P=0.008; 3.7 vs. 3.1 at 3 years, P =0.020).The HBsAg level at 6 months after treatment can help predict treatment response.
Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: The extended DACUS study
Authors: Sergio Siragusa, Alessandra Malato, Giorgia Saccullo, Alfonso Iorio, Mauro Di Ianni, Clementina Caracciolo, Lucio Lo Coco, Simona Raso, Marco Santoro, Francesco Paolo Guarneri, Antonino Tuttolomondo, Antonio Pinto, Iliana Pepe, Alessandra Casuccio, Vincenzo Abbadessa, Giuseppe Licata, Giovan Battista Rini, Guglielmo Mariani, Gaetana Di Fede
Journal: American Journal of Hematology (2011)

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.
Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression
Authors: John Shaughnessy, Joth Jacobson, Jeff Sawyer, Jason McCoy, Athanasios Fassas, Fenghuang Zhan, Klaus Bumm, Joshua Epstein, Elias Anaissie, Sundar Jagannath, David Vesole, David Siegel, Raman Desikan, Nikhil Munshi, Ashraf Badros, Erming Tian, Maurizio Zangari, Guido Tricot, John Crowley, Bart Barlogie
Journal: Blood (2003)
Expansion of necrotic core and shedding of Mertk receptor in human carotid plaques: a role for oxidized polyunsaturated fatty acids?
Authors: Ulisse Garbin, Elda Baggio, Chiara Stranieri, Andrea Pasini, Stefania Manfro, Chiara Mozzini, Paola Vallerio, Giovanni Lipari, Flavia Merigo, Giancesare Guidi, Luciano Cominacini, Anna Fratta Pasini
Journal: Cardiovascular Research (2012)

AimsExpansion of necrotic core (NC), a major feature responsible for plaque disruption, is likely the consequence of accelerated macrophage apoptosis coupled with defective phagocytic clearance (efferocytosis). The cleavage of the extracellular domain of Mer tyrosine kinase (Mertk) by metallopeptidase domain17 (Adam17) has been shown to produce a soluble Mertk protein (sMer), which can inhibit efferocytosis. Herein, we analysed the expression and localization of Mertk and Adam17 in the tissue around the necrotic core (TANC) and in the periphery (P) of human carotid plaques. Then we studied the mechanisms of NC expansion by evaluating which components of TANC induce Adam17 and the related cleavage of the extracellular domain of Mertk.
Characterization of the Ocular Phenotype of Duchenne and Becker Muscular Dystrophy
Authors: Dayle A. Sigesmund, Richard G. Weleber, De-Ann M. Pillers, Carol A. Westall, Carole M. Panton, Berkley R. Powell, Elise Héon, William H. Murphey, Maria A. Musarella, Peter N. Ray
Journal: Ophthalmology (1994)
Prevalence of the Night Eating Syndrome in a Psychiatric Population
Authors: Jennifer D. Lundgren, Kelly C. Allison, Scott Crow, John P. O’Reardon, Kelly C. Berg, Juliette Galbraith, Nicole S. Martino, Albert J. Stunkard
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: This study assessed the prevalence of night eating syndrome and its comorbid psychopathology in a psychiatric population. METHOD: The Night Eating Questionnaire was administered to 399 patients in two psychiatric outpatient clinics. Those scoring above 20 on the questionnaire (N=205) were assessed for night eating syndrome with a semistructured telephone interview. Chart reviews of all participants were performed to determine their psychiatric diagnoses and medications. RESULTS: Forty-nine participants (12.3%) met criteria for night eating syndrome. Greater rates of substance use disorders were found among patients diagnosed with night eating syndrome than among those without the syndrome. Obese patients were more likely than nonobese patients to manifest night eating syndrome. CONCLUSIONS: Night eating syndrome is prevalent among psychiatric clinic outpatients and is likely to co-occur with substance use disorders and obesity.
Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer.
Authors: D F Hayes, J A Van Zyl, A Hacking, L Goedhals, W R Bezwoda, J A Mailliard, S E Jones, C L Vogel, R F Berris, I Shemano
Journal: Journal of Clinical Oncology (1995)

PURPOSE To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer. MATERIALS AND METHODS Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212). RESULTS The combined response rates (by intent to treat) were as follows;: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms. CONCLUSION The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.
Oncogenic Kras Requires Simultaneous PI3K Signaling to Induce ERK Activation and Transform Thyroid Epithelial Cells <i>In vivo</i>
Authors: Kelly A. Miller, Nicole Yeager, Kristen Baker, Xiao-Hui Liao, Samuel Refetoff, Antonio Di Cristofano
Journal: Cancer Research (2009)

Thyroid tumors arising from the follicular cells often harbor mutations leading to the constitutive activation of the PI3K and Ras signaling cascades. However, it is still unclear what their respective contribution to the neoplastic process is, as well as to what extent they interact. We have used mice harboring a Kras oncogenic mutation and a Pten deletion targeted to the thyroid epithelium to address in vivo these questions. Here, we show that although each of these two pathways, alone, is unable to transform thyroid follicular cells, their simultaneous activation is highly oncogenic, leading to invasive and metastatic follicular carcinomas. In particular, phosphatidylinositol-3-kinase (PI3K) activation suppressed Kras-initiated feedback signals that uncouple mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) and ERK activation, thus stunting MAPK activity; in addition, PI3K and Kras cooperated to drastically up-regulate cyclin D1 mRNA levels. Finally, combined pharmacologic inhibition of PI3K and MAPK completely inhibited the growth of double-mutant cancer cell lines, providing a compelling rationale for the dual targeting of these pathways in thyroid cancer.
Glioma Proliferation as Assessed by 3‘-Fluoro-3’-Deoxy-<scp>l</scp>-Thymidine Positron Emission Tomography in Patients with Newly Diagnosed High-Grade Glioma
Authors: Roland Ullrich, Heiko Backes, Hongfeng Li, Lutz Kracht, Hrvoje Miletic, Kristina Kesper, Bernd Neumaier, Wolf-Dieter Heiss, Klaus Wienhard, Andreas H. Jacobs
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The aim of this study was to investigate the relationship between the in vivo derived kinetic parameters of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and the proliferation rate measured in vitro by Ki-67 staining in patients with newly diagnosed high-grade gliomas. Experimental Design: Thirteen patients with newly diagnosed high-grade gliomas were investigated with 18F-FLT and methyl-11C- l-methionine (11C-MET) positron emission tomography (PET) and T1-, Gd-T1–, and T2-weighted magnetic resonance imaging on consecutive days. Tracer kinetic parameters of 18F-FLT as well as the standardized uptake value and the tumor-to-background (T/B) ratio of 18F-FLT and 11C-MET were determined. Data of kinetic modeling, standardized uptake value, and T/B values derived from 18F-FLT-PET were compared with T/B values derived from 11C-MET-PET and to the in vitro proliferation marker Ki-67. Results: A significant correlation was observed between the metabolic rate constant Ki and the proliferation index as measured by Ki-67 immunostaining [Ki, r = 0.79 (P = 0.004)]. Also, the phosphorylation rate constant k3 correlated with Ki-67 [k3, r = 0.76 (P = 0.006)], whereas the rate constant for transport through the blood brain barrier K1 showed a weaker correlation with Ki-67 [K1, r = 0.62 (P = 0.044)]. No significant correlation between 11C-MET and 18F-FLT uptake ratios and Ki-67 was observed. Conclusions: This study shows that kinetic analysis of 18F-FLT tracer uptake is essential for the in vivo assessment of tumor proliferation in high-grade gliomas, whereas uptake ratios of 11C-MET and 18F-FLT failed to correlate with the in vitro determined proliferation marker. Thus, kinetic analysis of 18F-FLT might provide an accurate method for the assessment of early response to glioma treatment in the future.
Molecular mechanisms of hepatocellular carcinoma
Authors: Rajagopal N. Aravalli, Clifford J. Steer, Erik N. K. Cressman
Journal: Hepatology (2008)

Abstract Hepatocellular carcinoma (HCC) typically has poor prognosis, because it is often diagnosed at an advanced stage. Heterogeneous phenotypic and genetic traits of affected individuals and a wide range of risk factors have classified it a complex disease. HCC is not amenable to standard chemotherapy and is resistant to radiotherapy. In most cases, surgical resection and liver transplantation remain the only curative treatment options. Therefore, development of novel, effective therapies is of prime importance. Extensive research over the past decade has identified a number of molecular biomarkers as well as cellular networks and signaling pathways affected in liver cancer. Recent studies using a combination of “omics” technologies, microRNA studies, combinatorial chemistry, and bioinformatics are providing new insights into the gene expression and protein profiles during various stages of the disease. In this review, we discuss the contribution of these newer approaches toward an understanding of molecular mechanisms of HCC and for the development of novel cancer therapeutics. (Hepatology 2008;48:2047-2063.)
Insulin independence after living-donor distal pancreatectomy and islet allotransplantation
Authors: Shinichi Matsumoto, Teru Okitsu, Yasuhiro Iwanaga, Hirofumi Noguchi, Hideo Nagata, Yukihide Yonekawa, Yuichiro Yamada, Kazuhito Fukuda, Katsushi Tsukiyama, Haruhiko Suzuki, Yukiko Kawasaki, Makiko Shimodaira, Keiko Matsuoka, Toshiya Shibata, Yasunari Kasai, Taira Maekawa, AM James Shapiro, Koichi Tanaka
Journal: The Lancet (2005)