tbuckley/cabot-search huggingface dataset:
Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott syndrome.
Authors: H Kojima, D Newton-Nash, H J Weiss, J Zhao, P J Sims, T Wiedmer
Journal: Journal of Clinical Investigation (1994)

Scott syndrome is a bleeding disorder associated with an isolated defect in expression of membrane coagulant activity by stimulated platelets. This defect represents a decrease in platelet membrane binding sites for coagulation factors Va and VIIIa, reflecting diminished surface exposure of phosphatidylserine (PS). To gain insight into the cellular and genetic basis for this disorder, B-lymphocytes from a patient with Scott syndrome and from normal donors were immortalized by EBV-transformation, and tested for their capacity to expose plasma membrane PS in response to the Ca2+ ionophore, A23187. Upon incubation with A23187, EBV-lymphoblasts derived from normal donors consistently induced surface expression of PS in > 70% of all cells, as detected by membrane association of the PS-binding proteins, factor Va or annexin V. PS exposure in these cells was maximal after 5 min, and saturated at < 100 microM external free [Ca2+]. By contrast, < 30% of Scott syndrome lymphoblasts exposed PS, and saturation was not observed at > 1 mM external free [Ca2+]. Single-cell clones derived from the Scott lymphoblasts all exhibited a diminished response to A23187 comparable with that of the parental cells, suggesting that all lymphocytes from this patient share this membrane abnormality. Hybridomas prepared by fusion of Scott lymphoblasts with the myeloma cell line UC-LUC showed responses to Ca2+ ionophore comparable to those observed for normal lymphoblasts and for hybridomas prepared by fusion of normal lymphoblasts with UC-LUC. This correction of the Scott abnormality suggests possible complementation of an aberrant gene(s) responsible for this disorder.
Pathogenesis of Immunoglobulin A Nephropathy: Recent Insight from Genetic Studies
Authors: Krzysztof Kiryluk, Jan Novak, Ali G. Gharavi
Journal: Annual Review of Medicine (2012)

Recent genome-wide association studies (GWAS) have identified multiple susceptibility loci for immunoglobulin A nephropathy (IgAN), the most common form of glomerulonephritis, implicating independent defects in adaptive immunity (three loci on chromosome 6p21 in the MHC region), innate immunity (8p23 DEFA locus, 17p23 TNFSF13 locus, 22q12 HORMAD2 locus), and the alternative complement pathway (1q32 CFH/CFHR locus). In geospatial analysis of 85 populations, a genetic risk score based on the replicated GWAS loci is highest in Asians, intermediate in Europeans, and lowest in Africans, capturing the known difference in prevalence among world populations. The genetic risk score also uncovered a previously unsuspected increased prevalence of IgAN-attributable kidney failure in Northern Europe. The IgAN risk alleles have opposing effects on many immune-mediated diseases, suggesting that selection has contributed to variation in risk allele frequencies among different populations. Incorporating genetic, immunologic, and biochemical data, we present a multistep pathogenesis model that provides testable hypotheses for dissecting the mechanisms of disease.
Isolation of atypical HIV-1-related retrovirus from AIDS patient
Authors: H. Agut, B. Rabanel, D. Candotti, J.-M. Huraux, G. Remy, T. Tabary, D. Ingrand, C. Chippaux, S. Chamaret, C. Dauguet, D. Guetard, L. Montagnier
Journal: The Lancet (1992)
Detection and identification of antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing
Authors: I Peene
Journal: Annals of the Rheumatic Diseases (2001)

To provide data on (a) the probability of detecting antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing and (b) the probability of detecting more specific antinuclear reactivities (anti-DNA and anti-extractable nuclear antigens (anti-ENA)) in serum samples with a positive screening test (indirect immunofluorescence on HEp-2 cells).Serum samples from 10 550 consecutive patients sent to the laboratory for ANA detection were analysed. In ANA positive serum samples (23.5% of referred serum samples), ANA were identified by indirect immunofluorescence on Crithidia, by immunodiffusion, and by line immunoassay. Because anti-SSA antibodies were the most frequently identified ANA, sensitively detected by line immunoassay, additional immunoassays were developed to confirm the specificity of the line immunoassay result.At least one fine reactivity could be identified in 21.1% of ANA positive serum samples: anti-dsDNA in 3.2%; anti-ENA (anti-SSA 10.5%, anti-SSB 6.7%, anti-RNP 2.7%, anti-Sm 1.8%, anti-Scl70 1.2%, anti-Jo-1 0.2%) in 15.8%, rRNP and anti-Cenp-B in respectively 0.5% and 4.0%. Multiple reactivities were found in 7.9%. For anti-ENA antibodies, line immunoassay was more sensitive than immunodiffusion (15.4% v 7.7%; p<0.0001). The sensitive detection of anti-SSA antibodies by line immunoassay was confirmed by additional assays.The data from this analysis are useful in estimating the probabilities of detecting specific ANA. Line immunoassay was shown to be a sensitive test for the detection of anti-ENA antibodies.
Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs
Authors: J-L. Vanherweghem, C. Tielemans, D. Abramowicz, M. Depierreux, R. Vanhaelen-Fastre, M. Vanhaelen, M. Dratwa, C. Richard, D. Vandervelde, D. Verbeelen, M. Jadoul
Journal: The Lancet (1993)
Extreme variations in racial rates of total hip arthroplasty for primary coxarthrosis: a population-based study in San Francisco.
Authors: F T Hoaglund, C S Oishi, G G Gialamas
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To compare the incidence of all total hip arthroplasty, and total hip arthroplasty for primary coxarthrosis, among the Asian, black, Hispanic, and white populations living in one locale. METHODS--We identified all San Francisco residents who underwent total hip replacements (THR) in the 17 hospitals for adults within or near San Francisco County during a five year period. Preoperative pelvic radiographs were read without prior knowledge of the gender or race of the subject, to diagnose the specific hip diseases. Age standardised THR incidence by race and gender was determined, as was the comparative THR incidence for specific diagnosis (primary and secondary osteoarthritis). RESULTS--The greatest annual rate of total hip replacement occurred in white women (97 per 100,000 population), followed by white men, black women, black men, Hispanic women, and Hispanic men. The smallest numbers were found in Asians, whose THR rate was 10% that of whites. A primary coxarthrosis diagnosis was greatest among white subjects (66%), followed by black subjects (54%), Hispanics (53%), and Asians (28%). Age standardised THR rates for primary coxarthrosis per 100,000 population were likewise greatest among whites (43.0) and least among Asians (1.3 for Chinese). Mean age of patients undergoing THR for primary coxarthrosis was 70 years for white subjects and almost a decade younger in all other groups. CONCLUSIONS--THR rates are much lower for Asians, Hispanics, and black subjects than for the white population living in San Francisco. The low rates of total hip arthroplasty in the non-white groups was related to the much lower incidence of THR for primary coxarthrosis among non-whites than among whites. The racial distribution of primary coxarthrosis among patients who underwent THR is consistent with distribution patterns reported internationally.
Perindopril-associated pneumonitis
Authors: A Benard, B Melloni, B Gosselin, F Bonnaud, B Wallaert
Journal: European Respiratory Journal (1996)

We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect.
Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages.
Authors: S L Newman, J E Henson, P M Henson
Journal: The Journal of Experimental Medicine (1982)

An in vitro system to investigate the ability of macrophages to recognize and ingest senescent polymorphonuclear neutrophils has been used that uses chromium-labeled neutrophils and staining for myeloperoxidase (MPO). Human monocyte-derived macrophages obtained from in vitro cultures were able to recognize "aged" but not freshly isolated 51Cr-labeled human neutrophils and ingest them. Freshly isolated monocytes did not exhibit this property. Because the aged neutrophils were greater than 95% viable, death did not appear to be a prerequisite for recognition and ingestion. Serum was not required for the aging of the neutrophils, and when serum was used, different concentrations did not appear to effect the aging process; that is, neutrophils aged in different concentrations of serum were ingested equally. Phagocytosis of senescent neutrophils by macrophages occurred in a time-dependent manner and was also dependent on the number of neutrophils added. Monocyte-derived macrophages first exhibited the ability to phagocytose senescent neutrophils on the 3rd d of culture, with the percentage of active macrophages increasing through day 7. In experiments with rabbit mononuclear phagocytes, immune complex-induced inflammatory macrophages from the lung but not resident bronchoalveolar macrophages or peripheral blood monocytes were found to be capable of recognition and ingestion of senescent rabbit neutrophils. These data suggest that the monocyte maturation process, akin to that seen during inflammation, is necessary in vitro before macrophages recognize and remove senescent neutrophils.
The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib
Authors: David Masiello, Gerry Gorospe, Allen S Yang
Journal: Journal of Hematology & Oncology (2009)

Abstract Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusion risk factors should be monitored closely while taking dasatinib. Patients receiving imatinib and nilotinib are not without risk of fluid retention. All patients should also be educated to recognize and report key symptoms of fluid retention or pleural effusion. Pleural effusions are generally managed by dose interruption/reduction and other supportive measures in patients with chronic myeloid leukemia receiving dasatinib therapy.
Concomitant use of fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) as markers for predicting asthma exacerbation
Authors: Manabu Uematsu, Junpei Saito, Yasuhito Suzuki, Atsuro Fukuhara, Suguru Sato, Kenichi Misa, Yakefumi Nikaido, Naoko Fukuhara, Xintao Wang, Yoshinori Tanino, Takashi Ishida, Mitsuru Munakata
Journal: European Respiratory Journal (2014)

RATIONALE: FeNO became available in many countries for guiding asthma control as well as asthma diagnosis. However, it is unclear whether FeNO could be an adjunct for predicting asthma exacerbation.  OBJECTIVES: To analyse retrospectively the relationship between FeNO levels and asthma control test (ACT) scores with regard to the number of asthma exacerbation and adherence to the asthma treatment in the past one year.  METHODS: One hundred six asthmatic subjects were randomly selected from our database. All subjects were treated with inhaled corticosteroids (ICS).Subjects were classified into 4 groups based on FeNO levels of 40ppb and ACT scores of 20 points. Asthma exacerbation was defined as need of oral or parenteral corticosteroids.  RESULTS: Regardless of ACT scores, subjects with FeNO≥40ppb had experienced more exacerbations than those with FeNO  CONCLUSIONS:Even if asthma control assessed by ACT is good, subjects with higher FeNO levels are likely to have more exacerbations. Thus, concomitant use of FeNO and ACT could be useful to predict future risks of exacerbation.
Continuum of Cardiovascular Performance Across a Broad Range of Fitness Levels in Healthy Older Men
Authors: Steven P. Schulman, Jerome L. Fleg, Andrew P. Goldberg, Jan Busby-Whitehead, James M. Hagberg, Frances C. O'Connor, Gary Gerstenblith, Lewis C. Becker, Leslie I. Katzel, Loretta E. Lakatta, Edward G. Lakatta
Journal: Circulation (1996)

Background Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. Methods and Results Ten sedentary men (S), age 60.0±1.6 years (mean±SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (V̇ o 2max ) was 49.9±1.9 and 32.1±1.4 mL·kg −1 ·min −1 in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, V̇ o 2max fell to 42±2.2 mL·kg −1 ·min −1 , and training of S increased V̇ o 2max to 36.2±1.6 mL·kg −1 ·min −1 . Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (V̇ o 2max of 26 to 58 mL·kg −1 ·min −1 ), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with V̇ o 2max . Conclusions Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention.
Analysis of Micrometastatic Disease in Sentinel Lymph Nodes From Resectable Colon Cancer: Results of Cancer and Leukemia Group B Trial 80001
Authors: Mark Redston, Carolyn C. Compton, Brent W. Miedema, Donna Niedzwiecki, Jeannette M. Dowell, Scott D. Jewell, James M. Fleshman, Jiri Bem, Robert J. Mayer, Monica M. Bertagnolli
Journal: Journal of Clinical Oncology (2006)

To determine whether sentinel lymph node (LN) sampling (SLNS) could reduce the number of nodes required to characterize micrometastatic disease (MMD) in patients with potentially curable colon cancer.Cancer and Leukemia Group B 80001 was a study to determine whether SLNS could identify a subset of LNs that predicted the status of the nodal basin for resectable colon cancer and, therefore, could be extensively evaluated for the presence of micrometastases. Patients enrolled onto this study underwent SLNS after injection of 1% isosulfan blue, and both sentinel nodes (SNs) and non-SNs obtained during primary tumor resection were sectioned at multiple levels and stained using anti-carcinoembryonic antigen and anticytokeratin antibodies.Using standard histopathology, SNs failed to predict the presence of nodal disease in 13 (54%) of 24 node-positive patients. Immunostains were performed for patients whose LNs were negative by standard histopathology. Depending on the immunohistochemical criteria used to assign LN positivity, SN examination resulted in either an unacceptably high false-positive rate (20%) or a low sensitivity for detection of MMD (40%).By examining both SNs and non-SNs, this multi-institutional study showed that SNs did not accurately predict the presence of either conventionally defined nodal metastases or MMD. As a result, SLNS is not a useful technique for the study of MMD in patients with colon cancer.
Administration of Glucocorticoids to Ovarian Cancer Patients Is Associated with Expression of the Anti-apoptotic Genes <i>SGK1</i> and <i>MKP1/DUSP1</i> in Ovarian Tissues
Authors: Amal Melhem, S. Diane Yamada, Gini F. Fleming, Bertha Delgado, Deanna R. Brickley, Wei Wu, Masha Kocherginsky, Suzanne D. Conzen
Journal: Clinical Cancer Research (2009)

To prevent chemotherapy-related side effects, synthetic glucocorticoids, for example, dexamethasone, are routinely administered to patients with ovarian cancer. However, preclinical data implicate glucocorticoids in suppressing chemotherapy-mediated apoptosis in epithelial tumors. The anti-apoptotic mechanisms underlying this increased survival have been shown to require up-regulation of prosurvival genes, including serum and glucocorticoid-regulated kinase 1 (SGK1) and map kinase phosphatase 1 (MKP1)/dual specificity phosphatase 1 (DUSP1). Despite abundant preclinical data, there are no correlative studies in patients. We therefore evaluated anti-apoptotic gene expression in tumor samples from patients randomized to dexamethasone or normal saline.Eighteen patients were randomized before exploratory laparotomy for suspected ovarian cancer. Dexamethasone or normal saline was administered i.v. following anesthesia. Ovarian and omental tumor samples were collected intra-operatively before and after infusion. Samples were analyzed for histology and glucocorticoid receptor expression by immunohistochemistry. SGK1 and MKP1/DUSP1 mRNA levels were determined using quantitative real-time PCR.Ten patients were evaluable. At 30 min postinfusion, tumor samples from five patients receiving dexamethasone revealed an average SGK1 mRNA induction of 6.1-fold (SEM, +/-2.6) compared with only 1.5-fold (SEM, +/-0.4) in tumor samples from five patients receiving normal saline (P = 0.028). Average MKP1/DUSP1 mRNA expression was increased by 8.2-fold (SEM, +/-2.9) following dexamethasone versus 1.1-fold (SEM, +/-0.4) following normal saline (P = 0.009). All samples expressed glucocorticoid receptor.Glucocorticoid administration to patients is associated with rapid up-regulation of SGK1 and MKP1 expression in ovarian tumors. This finding supports the hypothesis that pharmacologic doses of glucocorticoids may decrease chemotherapy effectiveness in ovarian cancer patients through increased anti-apoptotic gene expression.
Effect of inspiratory pressure-threshold loading on the respiratory response to incremental exercise
Authors: Peter Habershon, Steve Draper, Stephen How
Journal: European Respiratory Journal (2014)

The impact of inspiratory threshold loading on constant load exercise has been examined using absolute exercise intensities (Carra, J. et al. Journal of Applied Physiology. 2003; 94: 2448-2455). However, breathing load may alter the work-rates at which VO2peak and gas exchange threshold (GET) occur. Therefore, the aim of this study was to determine the effect of threshold loading on the response to ramp exercise.  Twelve active males took part in this study. At separate visits (>48 hrs.) subjects performed maximal ramp cycle tests to determine VO2peak and GET with either no inspiratory resistance or threshold loads of 15 and 30 cmH2O. Breath-by-breath V  O2 data was modelled using a bi-exponential function. The effect of inspiratory load on the VO2 response to ramp exercise was determined with one way analysis of variance and post-hoc linear trend analysis.  During ramp exercise there were significant linear trends in GET (P=0.041) and peak power (P=0.002). There was no effect on VO2peak (P=0.719).  This study has shown that the work-rate at GET decreases as threshold-load increases. Therefore, studies investigating constant load exercise should consider the use of intensities relative to GET.
EFFECT OF STIMULATION OF THE LYMPHOCYTES ON THE RATE OF GROWTH OF SPONTANEOUS TUMORS IN MICE
Authors: James B. Murphy, Ernest Sturm
Journal: The Journal of Experimental Medicine (1919)

Spontaneous cancers were removed from a series of mice by operation. The animals were then subjected to an exposure to dry heat at a temperature ranging from 55–63°C. for 5 minutes. Immediately afterwards a graft of the original tumor was returned. The mice so treated exhibited a marked increase in their resistance to the growth of the cancer graft, over 59 per cent remaining entirely free from a return of the cancer. In a control series in which no treatment was given 96 per cent of the animals showed a return of the cancer.