tbuckley/cabot-search huggingface dataset:
Prospective Assessment of Discontinuation and Reinitiation of Erlotinib or Gefitinib in Patients with Acquired Resistance to Erlotinib or Gefitinib Followed by the Addition of Everolimus
Authors: Gregory J. Riely, Mark G. Kris, Binsheng Zhao, Tim Akhurst, Daniel T. Milton, Erin Moore, Leslie Tyson, William Pao, Naiyer A. Rizvi, Lawrence H. Schwartz, Vincent A. Miller
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Ten percent of U.S. patients with non–small cell lung cancer experience partial radiographic responses to erlotinib or gefitinib. Despite initial regressions, these patients develop acquired resistance to erlotinib or gefitinib. In these patients, we sought to assess changes in tumor metabolism and size after stopping and restarting erlotinib or gefitinib and to determine the effect of adding everolimus. Experimental Design: Patients with non–small cell lung cancer and acquired resistance to erlotinib or gefitinib were eligible. Patients had 18-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography and computed tomography scans at baseline, 3 weeks after stopping erlotinib or gefitinib, and 3 weeks after restarting erlotinib or gefitinib. Three weeks after restarting erlotinib or gefitinib, everolimus was added to treatment. Results: Ten patients completed all four planned studies. Three weeks after stopping erlotinib or gefitinib, there was a median 18% increase in SUVmax and 9% increase in tumor diameter. Three weeks after restarting erlotinib or gefitinib, there was a median 4% decrease in SUVmax and 1% decrease in tumor diameter. No partial responses (0 of 10; 95% confidence interval, 0-31%) were seen with the addition of everolimus to erlotinib or gefitinib. Conclusions: In patients who develop acquired resistance, stopping erlotinib or gefitinib results in symptomatic progression, increase in SUVmax, and increase in tumor size. Symptoms improve and SUVmax decreases after restarting erlotinib or gefitinib, suggesting that some tumor cells remain sensitive to epidermal growth factor receptor blockade. No responses were observed with combined everolimus and erlotinib or gefitinib. We recommend a randomized trial to assess the value of continuing erlotinib or gefitinib after development of acquired resistance.
Relationship Between Low Quality-of-Care Scores and HMOs' Subsequent Public Disclosure of Quality-of-Care Scores
Authors: Danny McCormick
Journal: JAMA (2002)

chasers of health insurance, 2 individual consumers, 3 and lawmakers 4,5 are seeking more information on the quality of health care.Recently, the President's Commission on Consumer Protection and Quality in the Health Care Industry called for widespread public disclosure of quality data by all health care provider organizations including health plans. 6][13][14] Public disclosure of data on quality by health maintenance organizations (HMOs), except those enrolling Medicare patients, is voluntary.In 1998, only 32.5% of all HMOs disclosed their scores on the National Committee for Quality Assurance (NCQA) Health Plan Employer Data and Information Set (HEDIS) measures, 15 the most widely used set of quality indicators.If health plans that refuse to disclose quality data provide inferior care, publicly available data would overstate the average quality of HMO care nationally and result in a distorted picture of how a given plan that discloses quality data compares with that average.Selective nondisclosure could also undermine public accountability and quality improvement efforts by weakening the impetus to improve quality.Despite the importance of this issue, no peer-reviewed studies have examined the relationship of HMO quality to willingness to disclose quality scores.We linked data for multiple years from the NCQA's annual Quality Compass databases to determine if withdrawal from public disclosure of HEDIS scores was related to an HMO's HEDIS performance 1 year earlier.
Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth
Authors: Maria Antonietta Casiraghi, Massimo De Paschale, Luisa Romanò, Renato Biffi, Agnese Assi, Giorgio Binelli, Alessandro Remo Zanetti
Journal: Hepatology (2004)

Long-term follow up studies of hepatitis C virus (HCV) infection rarely exceed 20-25 yr. We studied the outcome of HCV infection in 35-yr-old adults infected at birth (1968) through mini transfusions of blood. A retrospective-prospective study was carried out. The cohort included 31 individuals who were given mini blood transfusions (21-30 ml) collected from a donor subsequently revealed to be HCV infected. At enrollment (1998), 18 of 31 (58.1%) recipients had anti-HCV antibody and 16 (88.9%) of them were HCV-RNA positive. All viremic recipients and the infectious donor had the same genotype 1b. Sequence analysis of E1/E2 and NS5b regions, coupled with phylogenetic analysis, indicated that HCV isolates from donor/recipients were linked. Eleven of the 16 viremic recipients gave consent to liver biopsy. Nine had no fibrosis or mild portal fibrosis and 2 had either discrete (Ishak's staging 3) or marked (Ishak's staging 4) fibrosis. During the prospective follow-up period (1998-2003), 2 patients were given therapy, one of whom achieved sustained clinical and virologic response. A second biopsy, performed in 5 patients at a 5 yr interval, revealed no substantial modifications in 4 cases and progression from absence of fibrosis to mild portal fibrosis in the fifth. In conclusion, taking into account the limited study sample, these findings suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 yr of infection.
Mechanisms of autoantibody production in autoimmune MRL mice.
Authors: D S Pisetsky, G A McCarty, D V Peters
Journal: The Journal of Experimental Medicine (1980)

The quantitative expression of anti-DNA and anti-Sm antibodies has been investigated in autoimmune MRL-lpr/lpr and MRL-+/+ mice. Anti-Sm antibodies were detected in sera from 21/23 lpr/lpr and 10/16 +/+ mice, with individual animals showing striking variation in the time-course and magnitude of this autoantibody response. The peak antibody levels of the responding animals of each substrain did not differ significantly. For anti-DNA antibody, a different pattern of responsiveness was observed. Individual animals of each substrain produced very similar responses in terms of the magnitude and time-course of serum anti-DNA antibody. The differences in the peak levels of the two substrains were highly significant, with lpr/lpr mice demonstrating a much greater anti-DNA antibody response than +/+ mice. In lpr/lpr mice tested for both autoantibody systems, serum anti-DNA and anti-Sm antibodies showed distinct time-courses. These studies indicate that anti-DNA and anti-Sm antibodies are expressed independently in MRL mice, with the expression of anti-DNA, but not anti-Sm antibody markedly influenced by the presence of the 1pr gene. A fundamental difference in the mechanisms involved in the generation of anti-DNA and anti-Sm antibodies is suggested by the quantitative pattern of the two responses.
Molecular defect in the sickle erythrocyte skeleton. Abnormal spectrin binding to sickle inside-our vesicles.
Authors: O S Platt, J F Falcone, S E Lux
Journal: Journal of Clinical Investigation (1985)

Although functional abnormalities of the sickle erythrocyte membrane skeleton have been described, there is little quantitative data on the function of the proteins that compose the skeleton. We have examined the association of spectrin, the major skeletal protein, with ankyrin, its high-affinity membrane binding site, and found sickle erythrocytes to have markedly reduced binding. Binding is assayed by incubation of purified 125I-spectrin with spectrin-depleted inside-out vesicles (IOVs) and measurement of the label bound to IOVs. Sickle IOVs bind approximately 50% less ankyrin than do controls IOVs (P less than 0.001). Control experiments show that this reduced binding is not a function of faulty composition or orientation of sickle IOVs, or of reticulocytosis per se. Our least symptomatic patient has the highest binding capacity, suggesting that this abnormality may be related to clinical severity. This trend is supported by experiments showing that asymptomatic subjects with sickle trait, sickle cell anemia and high fetal hemoglobin, and sickle beta +-thalassemia have normal binding, whereas a symptomatic patient with sickle beta zero-thalassemia has abnormal binding. In contrast to what we see with ankyrin in situ on the IOV, when isolated and studied in solution, sickle ankyrin binds normally to spectrin. This discrepancy may be related to preferential purification of the normal ankyrin species or to an abnormal topography of the membrane near the spectrin attachment site. We hypothesize that sickle hemoglobin or perhaps the metabolic consequences of sickling damage the protein skeleton. This damage may alter the surface of the erythrocyte and result in abnormal cell-cell interactions which may be related to clinical severity.
<i>Schistosoma mansoni</i> secretes a chemokine binding protein with antiinflammatory activity
Authors: Philip Smith, Rosie E. Fallon, Niamh E. Mangan, Caitriona M. Walsh, Margarida Saraiva, Jon R. Sayers, Andrew N.J. McKenzie, Antonio Alcami, Padraic G. Fallon
Journal: The Journal of Experimental Medicine (2005)

The coevolution of humans and infectious agents has exerted selective pressure on the immune system to control potentially lethal infections. Correspondingly, pathogens have evolved with various strategies to modulate and circumvent the host's innate and adaptive immune response. Schistosoma species are helminth parasites with genes that have been selected to modulate the host to tolerate chronic worm infections, often for decades, without overt morbidity. The modulation of immunity by schistosomes has been shown to prevent a range of immune-mediated diseases, including allergies and autoimmunity. Individual immune-modulating schistosome molecules have, therefore, therapeutic potential as selective manipulators of the immune system to prevent unrelated diseases. Here we show that S. mansoni eggs secrete a protein into host tissues that binds certain chemokines and inhibits their interaction with host chemokine receptors and their biological activity. The purified recombinant S. mansoni chemokine binding protein (smCKBP) suppressed inflammation in several disease models. smCKBP is unrelated to host proteins and is the first described chemokine binding protein encoded by a pathogenic human parasite and may have potential as an antiinflammatory agent.
Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy
Authors: T El Gnaoui, J Dupuis, K Belhadj, J-P Jais, A Rahmouni, C Copie-Bergman, I Gaillard, M Diviné, I Tabah-Fisch, F Reyes, C Haioun
Journal: Annals of Oncology (2007)
KL1 Internal Repeat Mediates Klotho Tumor Suppressor Activities and Inhibits bFGF and IGF-I Signaling in Pancreatic Cancer
Authors: Lilach Abramovitz, Tamar Rubinek, Hagai Ligumsky, Shikha Bose, Iris Barshack, Camila Avivi, Bella Kaufman, Ido Wolf
Journal: Clinical Cancer Research (2011)

Klotho is a transmembrane protein which can be shed, act as a circulating hormone and modulate the insulin-like growth factor (IGF)-I and the fibroblast growth factor (FGF) pathways. We have recently identified klotho as a tumor suppressor in breast cancer. Klotho is expressed in the normal pancreas and both the IGF-I and FGF pathways are involved in pancreatic cancer development. We, therefore, undertook to study the expression and activity of klotho in pancreatic cancer.Klotho expression was studied using immunohistochemistry and quantitative RT-PCR. Effects of klotho on cell growth were assessed in the pancreatic cancer cells Panc1, MiaPaCa2, and Colo357, using colony and MTT assays and xenograft models. Signaling pathway activity was measured by Western blotting.Klotho expression is downregulated in pancreatic adenocarcinoma. Overexpression of klotho, or treatment with soluble klotho, reduced growth of pancreatic cancer cells in vitro and in vivo, and inhibited activation of the IGF-I and the bFGF pathways. KL1 is a klotho subdomain formed by cleavage or alternative splicing. Compared with the full-length protein, KL1 showed similar growth inhibitory activity but did not promote FGF23 signaling. Thus, its administration to mice showed favorable safety profile.These studies indicate klotho as a potential tumor suppressor in pancreatic cancer, and suggest, for the first time, that klotho tumor suppressive activities are mediated through its KL1 domain. These results suggest the use of klotho or KL1 as potential strategy for the development of novel therapeutic interventions for pancreatic cancer.
Mouse Embryonic Stem Cell–Derived Embryoid Bodies Generate Progenitors That Integrate Long Term into Renal Proximal Tubules In Vivo
Authors: Cécile Vigneau, Katalin Polgar, Gary Striker, Justine Elliott, Deborah Hyink, Odile Weber, Hans-Joerg Fehling, Gordon Keller, Christopher Burrow, Patricia Wilson
Journal: Journal of the American Society of Nephrology (2007)

The metanephric kidney is a mesodermal organ that develops as a result of reciprocal interactions between the ureteric bud and the blastema. The generation of embryonic stem (ES) cell-derived progenitors offers potential for regenerative therapies but is often limited by development of tumor formation. Because brachyury (T) denotes mesoderm specification, a mouse ES cell line with green fluorescence protein (GFP) knocked into the functional T locus as well as lacZ in the ROSA26 locus (LacZ/T/GFP) was used in cell selection and lineage tracing. In the absence of leukemia inhibitory factor, mouse ES cells give rise to embryoid bodies that can differentiate into mesoderm. Culture conditions were optimized (4 d, 10 ng/ml Activin-A) to generate maximal numbers of renal progenitor populations identified by expression of the specific combination of renal markers cadherin-11, WT-1, Pax-2, and Wnt-4. LacZ/T/GFP+ cells were further enriched by FACS selection. Five days after injection of LacZ/T/GFP+ cells into embryonic kidney explants in organ culture, beta-galactosidase immunohistochemistry showed incorporation into blastemal cells of the nephrogenic zone. After a single injection into developing live newborn mouse kidneys, co-localization studies showed that the LacZ/T/GFP+ cells were stably integrated into proximal tubules with normal morphology and normal polarization of alkaline phosphatase and aquaporin-1 for 7 mo, without teratoma formation. It is concluded that defined differentiation of ES cells into embryoid bodies with Activin-A and selection for T expression provides a means to isolate and purify renal proximal tubular progenitor cells with the potential for safe use in regenerative therapies.
Reduced gastric mucosal blood flow in patients with portal-hypertensive gastropathy
Authors: Tadashi Iwao, Atsushi Toyonaga, Motoki Ikegami, Kazuhiko Oho, Michihiro Sumino, Hiroshi Harada, Munenori Sakaki, Hiroyuki Shigemori, Toshichika Aoki, Kyuichi Tanikawa
Journal: Hepatology (1993)

Although congestive gastric mucosal circulation has been suggested in patients with portal-hypertensive gastropathy, whether it is due to "active" (overflow) or "passive" (stasis) congestion is not known. To answer this question, we assessed regional gastric mucosal blood flow with laser Doppler flowmetry in 57 patients with portal hypertension and 30 controls. Twelve patients had portal-hypertensive gastropathy of the antrum: in eight it was mild and in four it was severe. Portal-hypertensive gastropathy of the corpus was seen in 32 patients: it was mild in 24 and severe in 8. Thus prevalence of portal-hypertensive gastropathy was higher in the corpus than in the antrum (p < 0.01). In the antrum, gastric mucosal blood flow was significantly lower (p < 0.05) in patients with severe portal-hypertensive gastropathy (0.54 +/- 0.27 V) than in controls (1.12 +/- 0.44 V), whereas the values in patients without portal-hypertensive gastropathy (0.90 +/- 0.35 V) and with mild portal-hypertensive gastropathy (0.91 +/- 0.31 V) were not significantly different from the values in controls (p < 0.05 on one-way analysis of variance). In the corpus, gastric mucosal blood flow was significantly lower in patients with mild (0.75 +/- 0.25 V) or severe portal-hypertensive gastropathy (0.42 +/- 0.22 V) than in controls (1.16 +/- 0.37 V) (p < 0.01 and p < 0.01, respectively) whereas the value in patients without portal-hypertensive gastropathy (0.99 +/- 0.37 V) was not significantly different from values in controls (p < 0.01 on one-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)
Age of Methylphenidate Treatment Initiation in Children With ADHD and Later Substance Abuse: Prospective Follow-Up Into Adulthood
Authors: Salvatore Mannuzza, Rachel G. Klein, Nhan L. Truong, John L. Moulton, Erica R. Roizen, Kathryn H. Howell, Francisco X. Castellanos
Journal: American Journal of Psychiatry (2008)

Animal studies have shown that age at stimulant exposure is positively related to later drug sensitivity. The purpose of this study was to examine whether age at initiation of stimulant treatment in children with attention deficit hyperactivity disorder (ADHD) is related to the subsequent development of substance use disorders.
6 and 12 month outcomes following RePneu bronchoscopic lung volume reduction coil treatment
Authors: Zaid Zoumot, Samuel Kemp, Cielito Caneja, Rekha Caudhuri, Suveer Singh, Stephen Bicknell, Pallav Shah
Journal: European Respiratory Journal (2013)

ZZ and SK contributed equally  INTRODUCTION: The RePneu Lung Volume Reduction Coils (LVRCs) are nitinol devices implanted bronchoscopically using fluoroscopic guidance, and retake their original coiled shape as they are deployed.Around 10 LVRCs implanted in an emphysematous lobe reduce hyperinflation and gas trapping.  METHODS: The RESET trial randomised 23 emphysematous subjects with severe airflow obstruction and hyperinflation to LVRC treatment and 23 to best medical care (controls). LVRC treatments were unilateral and sequential with a 1 month interval between treatments. Assessments of lung function, 6 minute walk distance (6MWD) and St. George9s Respiratory Questionnaire (SGRQ) occurred at baseline,3,6 and 12 months following the final treatment. The 3 month primary endpoint results (previously reported) showed significant improvements in outcomes in the LVRC group compared to controls. Controls joined the treatment group and had LVRC treatment after completion of the control phase. NCT01334307.  RESULTS: 39 patients completed 6 months follow-up and had reduction in SGRQ (-7.1 points, p=0.0004), increase in 6MWD(56.3 m, p  CONCLUSION: Statistically and clinically meaningful benefits in quality of life, exercise capacity and pulmonary function in patients treated with LVRC coils persist 12 months after treatment.
Replication of measles virus in human lymphocytes.
Authors: T Hyypiä, P Korkiamäki, R Vainionpää
Journal: The Journal of Experimental Medicine (1985)

Replication of measles virus was restricted in human peripheral blood mononuclear cells (PBMC). However, in in vitro-infected, unstimulated cells, active synthesis of viral RNA and proteins occurred, while the release of infectious virus could not be detected. Stimulation with PHA caused a productive infection cycle comparable to the lytic infection. Replication of viral RNA was demonstrated in both T and B cells, and in both OKT4+- and OKT8+-depleted T cell subsets. The presence of measles virus RNA was detected in PBMC isolated from measles patients, and the production of the immunoreactive hemagglutinin protein was defective in these cells.
Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients.
Authors: P B Watkins, S A Murray, L G Winkelman, D M Heuman, S A Wrighton, P S Guzelian
Journal: Journal of Clinical Investigation (1989)

The major P-450IIIA gene family member present in human liver is HLp which, like its rat liver orthologue P-450p, is inducible by glucocorticoids and catalyzes erythromycin N-demethylation. To develop a practical method to estimate the amounts of HLp in patients [14C]N-methyl erythromycin was injected into rats that had been pretreated with dexamethasone or with inducers of other forms of cytochrome P-450. The rate of demethylation of this substrate, measured simply as 14CO2 in the breath, correlated well with the concentrations of immunoreactive P-450p protein (r = 0.70), holocytochrome P-450p (r = 0.70), or with erythromycin N-demethylase activity (r = 0.90) determined in the liver microsomes prepared from each rat. Next, [14C]N-methyl erythromycin was administered to 30 patients and there was a sixfold interindividual variation in breath 14CO2 production seemingly unrelated to medications, smoking status or age. However, the average breath test values were twofold greater in female as compared to male patients (P less than 0.01). Breath 14CO2 production rose in patients retested after treatment with the P-450IIIA inducers dexamethasone (P less than 0.05) or rifampicin (P less than 0.05) and was decreased after treatment with the HLp inhibitor triacetyloleandomycin (P less than 0.05). We conclude that the erythromycin breath test provides a convenient assay of P-450IIIA cytochromes in rats and in some patients.
Surgical treatment of congenital coronary artery fistula.
Authors: S John, W J Perianayagam, S Muralidharan, V Nandakumar, R Mansfield, S Krishnaswamy, I P Sukumar, G Cherian
Journal: Thorax (1981)

Six patients with congenital coronary artery fistula underwent successful corrective surgery. Precise diagnosis was established either by retrograde aortography or more recently by selective arteriography. The left coronary artery was involved in four and the right in two cases. The fistula communicated with the right ventricle in three and the right atrium in three subjects. The operative approach is dictated by the site of entry of the vessel into the cardiac chamber. The use of cardiopulmonary bypass for intracardiac repair allows accurate closure of the fistula thereby reducing the chances of recurrence. A follow-up of one to seven years showed that all patients are asymptomatic and leading normal lives.