tbuckley/cabot-search huggingface dataset:
Analyses of IgA1 hinge glycopeptides in IgA nephropathy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Authors: Y Hiki, A Tanaka, T Kokubo, H Iwase, J Nishikido, K Hotta, Y Kobayashi
Journal: Journal of the American Society of Nephrology (1998)

This study was performed to analyze the structural variety of O-glycans on the IgA1 hinge in IgA nephropathy (IgAN). The IgA1 fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated from 13 IgAN patients, eight healthy control subjects, and 11 patients with other primary glomerulonephritides by pyridylethylation, trypsin treatment, and Jacalin affinity chromatography. Because of the use of Jacalin, only the Gal beta 1-3GalNAc residue containing IgA was analyzed. The molecular weights (MW) of the IgA1 fragments treated by the following sequential treatment by exoglycosidases were estimated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: (1) Sialidase treatment: the MW of the two observed peaks A and B were compatible with (A) HP + 4GalNAc + 4Gal and (B) HP + 5GalNAc + 4Gal. (2) Sialidase and galactosidase: the MW of the two identified peaks a and b were consistent with (a) HP + 4GalNAc and (b) HP + 5GalNAc. (3) Sialidase, galactosidase, and alpha-N-acetylgalactosaminidase. All subjects revealed one peak, indicating the 33-mer IgA1 hinge peptide core. The intensity rate of peak B/A was significantly decreased in the IgAN group (mean +/- SD, 1.01 +/- 0.08) compared with the negative control subjects (healthy group, 1.15 +/- 0.06, P = 0.0048; other glomerulonephritis group, 1.13 +/- 0.10, P = 0.0049; Scheffe's F test). These results suggested the presence of a defect in the Gal and/or GalNAc residues in the IgA1 hinge glycopeptides in IgAN.
Molecular systematics and paleobiogeography of the South American sigmodontine rodents [published erratum appears in Mol Biol Evol 1998 Feb;15(2):224]
Authors: S. R. Engel, K. M. Hogan, J. F. Taylor, S. K. Davis
Journal: Molecular Biology and Evolution (1998)

The murid rodent subfamily Sigmodontinae contains 79 genera which are distributed throughout the New World. The time of arrival of the first sigmodontines in South America and the estimated divergence time(s) of the different lineages of South American sigmodontines have been controversial due to the lack of a good fossil record and the immense number of extant species. The "early-arrival hypothesis" states that the sigmodontines must have arrived in South America no later than the early Miocene, at least 20 MYA, in order to account for their vast present-day diversity, whereas the "late-arrival hypothesis" includes the sigmodontines as part of the Plio-Pleistocene Great American Interchange, which occurred approximately 3.5 MYA. The phylogenetic relationships among 33 of these genera were reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3, ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the same rate. A molecular clock was calibrated for these genes using published fossil dates, and the genetic distances were estimated from the DNA sequences in this study. The molecular clock was used to estimate the dates of the South American sigmodontine origin and the main sigmodontine radiation in order to evaluate the "early-" and "late-arrival" scenarios. We estimate the time of the sigmodontine invasion of South America as between approximately 5 and 9 MYA, supporting neither of the scenarios but suggesting two possible models in which the invading lineage was either (1) ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to the akodonts and phyllotines and accompanied by the oryzomyines. The sigmodontine invasion of South America provides an example of the advantage afforded to a lineage by the fortuitous invasion of a previously unexploited habitat, in this case an entire continent.
Intrapulmonary distribution of 99mtechnetium labelled ultrafine carbon aerosol (Technegas) in severe airflow obstruction
Authors: AB Crawford, A Davison, TC Amis, LA Engel
Journal: European Respiratory Journal (1990)

Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTechnetium (99mTc), has been recently introduced for clinical imaging of lung ventilation. In 12 selected subjects with severe chronic airflow limitation (FEV1 = 0.89 +/- 0.22; mean +/- SD, l) we have studied the regional intrapulmonary distribution of TG and compared it quantitatively with that of 133Xenon (133Xe). A 133Xe equilibration image was acquired for 10-15 s during a breathhold at total lung capacity (TLC). Six subjects (Group 1) inspired 100 ml boli of TG or 133Xe from functional residual capacity (FRC) and another 6 subjects (Group 2) inspired 1.0 l of labelled gas from FRC followed by air to TLC at a constant flow rate less than 0.5 l.s-1. Lung images were then acquired with the chest position rigorously controlled. From the equilibration image, upper, middle, lower, central and peripheral regions were defined. Relative regional fractional concentrations (RFC) were then calculated using the equilibration image to correct for ventilated lung volume. In addition, in four of the Group 2 subjects, each lung image was divided into multiple regions (12-17 per lung). The RFC were then calculated as above (RFCM). The highest and lowest RFC were not significantly different between 133Xe and TG in either Group 1 or Group 2 subjects. Similarly the RFCM analysis showed no systematic difference between 133Xe and TG. The ratio of peripheral to central RFC constitutes a penetration index which for TG was 0.99 +/- 0.23 that of 133Xe. Our results indicate that even in the presence of severe airflow limitation the radiolabelled tracer TG mimics the regional distribution of a real gas.
Effect of Rosiglitazone Versus Insulin on the Pancreatic β-Cell Function of Subjects With Type 2 Diabetes
Authors: Fernando Ovalle, David S.H. Bell
Journal: Diabetes Care (2004)

OBJECTIVE—In a previous study, we found observational evidence of improvement in β-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study. RESEARCH DESIGN AND METHODS—A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide. RESULTS—Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA1c was well matched between groups before treatment (8.7 ± 0.3 and 9.0 ± 0.3%; NS) and at the end of the 6 months (7.8 ± 0.5 and 7.8 ± 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 μIU · ml−1 · 10 min−1; P &amp;lt; 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group. CONCLUSIONS—Rosiglitazone, but not insulin, induced a recovery of pancreatic β-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.
Effect of aminophylline on the human diaphragm.
Authors: J Moxham, J Miller, C M Wiles, A J Morris, M Green
Journal: Thorax (1985)

The effect of intravenous aminophylline on the contractile function of the diaphragm was studied in four normal subjects. The contractility of the diaphragm was assessed by the measurement of transdiaphragmatic pressure (Pdi) after right phrenic nerve stimulation at 1 Hz. Pdi was measured before and during aminophylline infusion (6 mg/kg over 30 minutes), during which therapeutic concentrations of theophylline were attained (mean 13.8 mg/l, range 8.5-20.2). The Pdi achieved was not affected by aminophylline. This result suggests that theophylline at therapeutic concentrations has little effect on the contractility of the normal human diaphragm.
Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients
Authors: A. Planck, A. Eklund, J. Grunewald
Journal: European Respiratory Journal (2003)

Scandinavian human leukocyte antigen-DR17-positive (DR17+) sarcoidosis patients are characterised by a good prognosis. They also reveal an accumulation in bronchoalveolar lavage fluid of T‐lymphocytes expressing the T‐cell receptor V gene segment AV2S3 at disease onset. The authors of this study wished to establish whether AV2S3 T‐lymphocyte accumulation changes from disease onset to clinically resolved disease and how this relates to other activity parameters. Bronchoalveolar lavage fluid and serum from nine DR17+ sarcoidosis patients were examined at disease onset and after spontaneous resolution of clinical and radiographical signs of disease. Nine DR17+ patients with lung accumulated CD4+ AV2S3+ T‐cells were investigated after clinically recovery. At re-examination the percentage of CD4+ AV2S3+ lymphocytes in bronchoalveolar lavage fluid was normalised (29 versus 5.4%). A significant reduction in lymphocyte percentage (14 versus 4.4%) and a decrease in cellular concentration (179×10 6 ·L −1 versus 111×10 6 ·L −1 ) and CD4/CD8 ratio (5.2 versus 2.4) were also seen. In serum, the activity of angiotensin-converting enzyme (24.9 versus 14.0 U·mL −1 ) as well as the levels of neopterin (7.8 versus 5.3 nmol·L −1 ) decreased significantly after recovery. These results indicate that the locally accumulated AV2S3 positive T‐lymphocytes in bronchoalveolar lavage are involved in the pathogenic process of sarcoidosis in this patient group.
Current status of fluoroquinolone use for treatment of tuberculosis in Korea
Authors: Bo Hyoung Kang, Tae Sun Shim, Sang-Do Lee, Woo Sung Kim, Dong Soon Kim
Journal: European Respiratory Journal (2013)

Introduction:  The fluoroquinolone (FQN) is an important substitute for treatment of multidrug-resistant tuberculosis (MDR-TB). However, the detailed information about FQN use in the treatment of TB is not available yet.   Aims and Objects : The aim of this study was to evaluate the current status of FQN use for treatment of TB.   Methods : A retrospective analysis was performed for 953 patients diagnosed with TB at one tertiary referral center in 2009.   Results : Among 953 patients, 220 patients (23.0%) received FQNs for anti-TB purpose. MDR-TB was present in 8.8-% (37/220) of patients. The mean age of 220 patients was 51.1 years old and male was predominant (54.5%). The most common reason for FQN use was adverse events of other anti-TB drugs (53.8%), followed by drug resistance (22.7%), and underlying liver or renal diseases (16.4%). Moxifloxacin (54.1%, 119/220) was the most common type of FQN, followed by levofloxacin (35.9%, 79/220) and ofloxacin (10.0%, 22/220). The median duration of FQN use was 236 days. The frequency of total adverse events from anti-TB medication was 23.2% and that from FQN was expected to be 9.5%. The most common FQN-related adverse event was gastrointestinal problems (3.6%, 8/220). There were no significant differences in the treatment success rate (80.0% vs. 78.4%) between FQN-used and FQN-naive groups.   Conclusion : In Korea, an intermediate TB-burden country, FQN is commonly used in the treatment of TB, especially as a substitute for adverse event-related drugs, and also for the treatment of MDR-TB. Considering the low adverse event rate and the comparable treatment success rate, FQN is an invaluable drug for the treatment of TB.
The low-affinity receptor for IgE (CD23) on B lymphocytes is spatially associated with HLA-DR antigens.
Authors: J Y Bonnefoy, O Guillot, H Spits, D Blanchard, K Ishizaka, J Banchereau
Journal: The Journal of Experimental Medicine (1988)

Two hybridomas that produce the mAbs 135 and 449 B4 were obtained that inhibited the binding of IgE to the Fc epsilon RL/CD23 on the EBV-transformed B cell line RPMI 8866. mAb 135 was obtained from a mouse immunized with RPMI 8866 cells, whereas mAb 449B4 was obtained from a mouse immunized with a partially purified preparation of Fc epsilon RL/CD23 obtained as the eluate of an IgE immunoabsorbent loaded with a soluble extract of RPMI 8866 cells. These two mAbs bound to Fc epsilon RL/CD23- cell lines and precipitated two polypeptides with 36,000 Mr and 28,000 Mr, which were the HLA-DR alpha and beta chains, respectively. Immunoprecipitation with mAb 135 of NP-40 lysates from dithio-bis(succinimidyl propionate) (DSP) crosslinked 125I-labeled RPMI 8866 or normal B cells incubated with rIL-4 showed three polypeptides with 42,000, 36,000, and 28,000 Mr. The 42,000 Mr polypeptide is identical to the Fc epsilon RL/CD23 since it could be precipitated by the anti-Fc epsilon RL/CD23 mAb 25 after resolubilization from the SDS-PAGE gel. Immunoprecipitations of the crosslinked cell extracts carried out with the anti-Fc epsilon RL/CD23 mAb 25 yielded the same three polypeptides. Furthermore, when RPMI 8866 or rIL-4 preincubated normal B cells were solubilized with a digitonin buffer, which prevents the dissociation of noncovalently linked polypeptide complexes, mAb 135 and mAb 25 precipitated complexes composed of three molecules with 42,000, 36,000, and 28,000 Mr. The well-characterized anti-HLA-DR mAb L243 was unable to block the binding of either IgE or mAb 135 to RPMI 8866 cells, although it could immunoprecipitate the complex (HLA-DR-Fc epsilon RL/CD23) from crosslinked cell lysates. Since mAb 135 and L243 were able to both bind the RPMI 8866 cells, it demonstrates that they bind to different epitopes of the HLA-DR complex, the mAb 135 epitope of the HLA-DR molecule being close to the IgE binding site of the Fc epsilon RL/CD23. These data demonstrated that the Fc epsilon RL/CD23 and HLA-DR antigens are spatially associated on the B cell membrane.
Survival Benefits With Diverse Chemotherapy Regimens for Ovarian Cancer: Meta-analysis of Multiple Treatments
Authors: Maria Kyrgiou, Georgia Salanti, Nicholas Pavlidis, Evangelos Paraskevaidis, John P. A. Ioannidis
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Numerous randomized trials have compared different chemotherapy regimens in women with ovarian cancer. Although ovarian cancer survival has improved in recent years, the magnitude of these incremental benefits across diverse regimens is unclear. Methods: We used multiple-treatment meta-analysis methodology to combine information from direct and indirect comparisons of all chemotherapy regimens used in randomized trials of ovarian cancer in the last 40 years. Chemotherapy was categorized by the use or not of platinum and/or taxanes, combinations of agents, and intraperitoneal administration. Monte Carlo simulations were used to determine which regimen most improved survival. Analyses of trials that examined first- and second-line treatments were also performed separately. Results: We found 198 trials (N = 38 440 women) involving 120 different chemotherapy regimens published in 1971–2006. Eighty-two trials compared different types of chemotherapy, among which 60 had usable survival information (N = 15 609 women). Monte Carlo simulations showed a 92% probability that the regimen that best prolonged survival is a platinum and taxane combination with intraperitoneal administration; this regimen resulted in a 55% relative risk reduction (95% confidence interval [CI] = 39% to 67%) for mortality as compared with nonintraperitoneal monotherapy using neither platinum nor taxane. Against that same monotherapy comparator, platinum-based combinations with and without intraperitoneal administration achieved 40% (95% CI = 21% to 54%) and 30% (95% CI = 20% to 38%) relative risk reductions for mortality, respectively, and combinations involving platinum and taxane without intraperitoneal administration achieved a 42% (95% CI = 31% to 51%) relative risk reduction. Results were similar when analyses were limited to first-line treatment. Data on second-line treatment were consistent with the superiority of platinum and taxane combinations. Conclusions: Distinct incremental improvements in survival have been achieved for ovarian cancer chemotherapy over time, with the possibility to achieve a doubling or more of time to mortality with platinum and taxane combinations, especially when intraperitoneal administration is used.
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells
Authors: L. Cen, B. L. Carlson, M. A. Schroeder, J. L. Ostrem, G. J. Kitange, A. C. Mladek, S. R. Fink, P. A. Decker, W. Wu, J.-S. Kim, T. Waldman, R. B. Jenkins, J. N. Sarkaria
Journal: Neuro-Oncology (2012)

Deregulation of the p16INK4a-Cdk4/6-Rb pathway is commonly detected in patients with glioblastoma multiforme (GBM) and is a rational therapeutic target. Here, we characterized the p16INK4a-Cdk4/6-Rb pathway in the Mayo panel of GBM xenografts, established from primary tissue samples from patients with GBM, and evaluated their response to PD0332991, a specific inhibitor of Cdk4/6. All GBM xenograft lines evaluated in this study had disruptions in the p16INK4a-Cdk4/6-Rb pathway. In vitro evaluation using short-term explant cultures from selected GBM xenograft lines showed that PD0332991 effectively arrested cell cycle in G1-phase and inhibited cell proliferation dose-dependently in lines deleted for CDKN2A/B-p16INK4a and either single-copy deletion of CDK4 (GBM22), high-level CDK6 amplification (GBM34), or deletion of CDKN2C/p18INK4c (GBM43). In contrast, 2 GBM lines with p16INK4a expression and either CDK4 amplification (GBM5) or RB mutation (GBM28) were completely resistant to PD0332991. Additional xenograft lines were screened, and GBM63 was identified to have p16INK4a expression and CDK4 amplification. Similar to the results with GBM5, GBM63 was resistant to PD0332991 treatment. In an orthotopic survival model, treatment of GBM6 xenografts (CDKN2A/B-deleted and CDK4 wild-type) with PD0332991 significantly suppressed tumor cell proliferation and prolonged survival. Collectively, these data support the concept that GBM tumors lacking p16INK4a expression and with nonamplified CDK4 and wild-type RB status may be more susceptible to Cdk4/6 inhibition using PD0332991.
Cryptogenic Bronchial Stenosis
Authors: Horiana B. Grosu, Carlos A. Jimenez, Rodolfo C. Morice, David Ost, Mona G. Sarkiss, George A. Eapen
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

A 52-year-old female with a reported history of lupus erythematosus (LE) diagnosed 20 years previously on the basis of arthralgia, discoid skin rash, and elevated serum antinuclear autoantibodies was referred for airway obstruction.The patient described increasing dyspnea and wheezing over a 10-year period.Chest computer tomography showed focal tracheal narrowing and significant narrowing of the right mainstem bronchus (Figures 1 and2).Bronchoscopy showed a stricture in the lower trachea and a discrete more severe stricture involving the right mainstem bronchus (Figure 1).Both strictures were dilated with complete symptom relief.Tracheobronchial strictures can result from trauma, inhalation injury, radiation, infections, and certain autoimmune diseases.This patient did not have any such history except for the LE.To our knowledge, bronchial stenosis has not been reported in association with LE.
Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease
Authors: WASIM MAZIAK, STELIOS LOUKIDES, SARAH CULPITT, PAUL SULLIVAN, SERGEI A. KHARITONOV, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investigated whether the concentration of exhaled NO is related to the severity of disease as defined by lung function. We also investigated whether concentration of exhaled NO was different in COPD patients who received inhaled steroids compared with steroid-naı̈ve patients. We studied 13 current smokers with COPD, eight exsmokers with COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10 smokers with chronic bronchitis without airflow limitation. Exhaled NO levels were significantly higher in patients with unstable COPD (12.7 ± 1.5 ppb) than in other groups (p < 0.01). Exhaled NO levels were significantly higher in smokers with COPD than in smokers with chronic bronchitis (4.3 ± 0.5 versus 2.5 ± 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had stopped smoking (6.3 ± 0.6 ppb, p < 0.01). Exhaled NO levels showed a significant negative correlation with their lung function assessed by % predicted FEV1 values (r = − 0.6, p < 0.001). Exhaled NO levels in patients treated with inhaled steroids were significantly higher compared with steroid-naı̈ve patients (8.2 ± 1.2 ppb versus 5 ± 0.4 ppb, p < 0.05), but the first group included more severe patients as assessed by lung function. We conclude that exhaled NO could serve as a useful, practical marker for monitoring disease activity in COPD.